A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment

La tri-metilación de la lisina 9 de la histona 3 (H3K9me3) es una modificación epigenética requerida para la formación y el mantenimiento de la heterocromatina, la estabilidad genómica y el silenciamiento de elementos transposables en células madre embrionarias (CMEs). SETDB1 es una metiltransferasa...

Full description

Autores:

Tipo de recurso:

Fecha de publicación:: 2018

Institución:: Universidad del Rosario

Repositorio:: Repositorio EdocUR - U. Rosario

Idioma:: eng

id	EDOCUR2_fd43d89e7dd9e1a0fb81b4891535d8ea
oai_identifier_str	oai:repository.urosario.edu.co:10336/19828
network_acronym_str	EDOCUR2
network_name_str	Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.eng.fl_str_mv	A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment
dc.title.TranslatedTitle.spa.fl_str_mv	Un mecanismo de transmetilación entre las dos principales metiltransferasas H3K9 SETDB1 y SUV39H1 regula el establecimiento de heterocromatina
dc.title.TranslatedTitle.fre.fl_str_mv	Un mécanisme de trans-méthylation entre les deux principales méthyltransférases de H3K9 SETDB1 et SUV39H1, régule l'établissement de l'hétérochromatine
title	A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment
spellingShingle	A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment Epigénesis Genética Evolución & genética SETDB1 SUV39H1 Lysine methylation Post-translational modification Embryonic stems cells SETDB1 SUV39H1 Metilación de lisinas Modificaciones post-traduccionales Células madre embrionarias
title_short	A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment
title_full	A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment
title_fullStr	A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment
title_full_unstemmed	A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment
title_sort	A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment
dc.contributor.advisor.none.fl_str_mv	Ait-Si-Ali, Slimane Ramírez Clavijo, Sandra Rocío
dc.subject.spa.fl_str_mv	Epigénesis Genética
topic	Epigénesis Genética Evolución & genética SETDB1 SUV39H1 Lysine methylation Post-translational modification Embryonic stems cells SETDB1 SUV39H1 Metilación de lisinas Modificaciones post-traduccionales Células madre embrionarias
dc.subject.ddc.spa.fl_str_mv	Evolución & genética
dc.subject.keyword.spa.fl_str_mv	SETDB1 SUV39H1 Lysine methylation Post-translational modification Embryonic stems cells
dc.subject.lemb.spa.fl_str_mv	SETDB1 SUV39H1 Metilación de lisinas Modificaciones post-traduccionales Células madre embrionarias
description	La tri-metilación de la lisina 9 de la histona 3 (H3K9me3) es una modificación epigenética requerida para la formación y el mantenimiento de la heterocromatina, la estabilidad genómica y el silenciamiento de elementos transposables en células madre embrionarias (CMEs). SETDB1 es una metiltransferasa específica de la lisina 9 de la histona 3 crucial durante el desarrollo de los mamíferos debido a que regula la pluripotencia de las CMEs en el embrión. Los resultados de este trabajo sugieren que SETDB1 lleva a cabo un proceso de auto-metilación que es requerido para el mantenimiento de la pluripotencia, el crecimiento y la viabilidad de las CMEs murinas. Adicionalmente, análisis de transcriptoma completo (RNA-seq) mostraron que la integridad de las dos lisinas auto-metiladas es requerida para el silenciamiento tanto de genes codificantes como de elementos transposables. De hecho, análisis de ChIP-seq revelaron que una deficiencia en la auto-metilación conlleva a una disminución en el establecimiento de H3K9me3 en loci blanco. Nuestros resultados sugieren que la auto-metilación de SETDB1 es un pre-requisito para la trans-metilación por SUV39H1. Este mecanismo podría regular no solamente la interacción física entre SETDB1 y SUV39H1 (vía el cromodominio de SUV39H1), sino también la cooperación para el establecimiento y el mantenimiento de la heterocromatina y el silenciamiento de los elementos transposables. Por todo lo anterior, los resultados de este trabajo revelan un nuevo mecanismo que regula las funciones de SETDB1, el cual es crucial para la identidad y el mantenimiento de las CMEs.
publishDate	2018
dc.date.created.none.fl_str_mv	2018-09-21
dc.date.issued.none.fl_str_mv	2018
dc.date.accessioned.none.fl_str_mv	2019-06-04T20:50:36Z
dc.date.available.none.fl_str_mv	2019-06-04T20:50:36Z
dc.type.eng.fl_str_mv	doctoralThesis
dc.type.coar.fl_str_mv	http://purl.org/coar/resource_type/c_db06
dc.type.document.spa.fl_str_mv	Trabajo de grado
dc.type.spa.spa.fl_str_mv	Tesis de doctorado
dc.identifier.doi.none.fl_str_mv	https://doi.org/10.48713/10336_19828
dc.identifier.uri.none.fl_str_mv	http://repository.urosario.edu.co/handle/10336/19828
url	https://doi.org/10.48713/10336_19828 http://repository.urosario.edu.co/handle/10336/19828
dc.language.iso.none.fl_str_mv	eng
language	eng
dc.rights.spa.fl_str_mv	Atribución-NoComercial-SinDerivadas 2.5 Colombia
dc.rights.coar.fl_str_mv	http://purl.org/coar/access_right/c_abf2
dc.rights.acceso.spa.fl_str_mv	Abierto (Texto Completo)
dc.rights.uri.none.fl_str_mv	http://creativecommons.org/licenses/by-nc-nd/2.5/co/
rights_invalid_str_mv	Atribución-NoComercial-SinDerivadas 2.5 Colombia Abierto (Texto Completo) http://creativecommons.org/licenses/by-nc-nd/2.5/co/ http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv	application/pdf
dc.publisher.spa.fl_str_mv	Universidad del Rosario
dc.publisher.department.spa.fl_str_mv	Facultad de Ciencias Naturales y Matemáticas
dc.publisher.program.spa.fl_str_mv	Doctorado en Ciencias Biomédicas
institution	Universidad del Rosario
dc.source.bibliographicCitation.spa.fl_str_mv	Fritsch L, Robin P, Mathieu JRR, Souidi M, Hinaux H, Rougeulle C, et al. A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Mol Cell [Internet]. 2010 Jan 15;37(1):46–56. Ishimoto K, Kawamata N, Uchihara Y, Okubo M, Fujimoto R, Gotoh E, et al. Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity. PLoS One [Internet]. 2016;11(10):e0165766. Yeap L-S, Hayashi K, Surani MA. ERG-associated protein with SET domain (ESET)-Oct4 interaction regulates pluripotency and represses the trophectoderm lineage. Epigenetics Chromatin [Internet]. 2009;2(1):12. Bilodeau S, Kagey MH, Frampton GM, Rahl PB, Young RA. SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state. Genes Dev [Internet]. 2009 Nov 1;23(21):2484–9. Dodge JE, Kang Y-K, Beppu H, Lei H, Li E. Histone H3-K9 methyltransferase ESET is essential for early development. Mol Cell Biol [Internet]. 2004 Mar;24(6):2478–86. Binda O, LeRoy G, Bua DJ, Garcia BA, Gozani O, Richard S. Trimethylation of histone H3 lysine 4 impairs methylation of histone H3 lysine 9: regulation of lysine methyltransferases by physical interaction with their substrates. Epigenetics [Internet]. 5(8):767–75. Fei Q, Shang K, Zhang J, Chuai S, Kong D, Zhou T, et al. Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53. Nat Commun [Internet]. 2015;6:8651. Hwang YJ, Han D, Kim KY, Min S-J, Kowall NW, Yang L, et al. ESET methylates UBF at K232/254 and regulates nucleolar heterochromatin plasticity and rDNA transcription. Nucleic Acids Res [Internet]. 2014 Feb;42(3):1628–43. Loyola A, Tagami H, Bonaldi T, Roche D, Quivy JP, Imhof A, et al. The HP1alpha-CAF1-SetDB1-containing complex provides H3K9me1 for Suv39-mediated K9me3 in pericentric heterochromatin. EMBO Rep [Internet]. 2009 Jul;10(7):769–75. Towbin BD, González-Aguilera C, Sack R, Gaidatzis D, Kalck V, Meister P, et al. Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell [Internet]. 2012 Aug 31;150(5):934–47. Bulut-Karslioglu A, De La Rosa-Velázquez IA, Ramirez F, Barenboim M, Onishi-Seebacher M, Arand J, et al. Suv39h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells. Mol Cell [Internet]. 2014 Jul 17;55(2):277–90. Baylin SB, Jones PA. A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer [Internet]. 2011 Oct;11(10):726–34. Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet [Internet]. 2012 Apr 3;13(5):343–57. Ding J, Li T, Wang X, Zhao E, Choi J-H, Yang L, et al. The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. Cell Metab [Internet]. 2013 Dec 3;18(6):896–907. Ceol CJ, Houvras Y, Jane-Valbuena J, Bilodeau S, Orlando DA, Battisti V, et al. The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature [Internet]. 2011 Mar 24;471(7339):513–7. Rodriguez-Paredes M, Martinez de Paz A, Simó-Riudalbas L, Sayols S, Moutinho C, Moran S, et al. Gene amplification of the histone methyltransferase SETDB1 contributes to human lung tumorigenesis. Oncogene [Internet]. 2014 May 22;33(21):2807–13. Liu L, Kimball S, Liu H, Holowatyj A, Yang Z-Q. Genetic alterations of histone lysine methyltransferases and their significance in breast cancer. Oncotarget [Internet]. 2015 Feb 10;6(4):2466–82. Burns KH, Boeke JD. Human transposon tectonics. Cell [Internet]. 2012 May 11;149(4):740–52. Waddington CH. The epigenotype. Endeavour. 1942;1:18. Baxter E, Windloch K, Gannon F, Lee JS. Epigenetic regulation in cancer progression. Cell Biosci [Internet]. 2014;4:45. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature [Internet]. 2004 May 27;429(6990):457–63. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res [Internet]. 2011 Mar;21(3):381–95. Saksouk N, Simboeck E, Déjardin J. Constitutive heterochromatin formation and transcription in mammals. Epigenetics Chromatin [Internet]. 2015;8:3. Grewal SIS, Jia S. Heterochromatin revisited. Nat Rev Genet [Internet]. 2007 Jan;8(1):35–46. Nishibuchi G, Déjardin J. The molecular basis of the organization of repetitive DNA-containing constitutive heterochromatin in mammals. Chromosome Res [Internet]. 2017 Mar;25(1):77–87. Wang J, Jia ST, Jia S. New Insights into the Regulation of Heterochromatin. Trends Genet [Internet]. 2016;32(5):284–94. Martin C, Zhang Y. The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol [Internet]. 2005 Nov;6(11):838–49. Jenuwein T, Allis CD. Translating the histone code. Science [Internet]. 2001 Aug 10;293(5532):1074–80. Ronner P. Netter’s Essential Biochemistry. First edit. Elsevier Health Sciences; 2016. 43 p. Felsenfeld G, Groudine M. Controlling the double helix. Nature [Internet]. 2003 Jan 23;421(6921):448–53. Bhaumik SR, Smith E, Shilatifard A. Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol [Internet]. 2007 Nov;14(11):1008–16. Huynh JL, Casaccia P. Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol [Internet]. 2013 Feb;12(2):195–206. Mozzetta C, Boyarchuk E, Pontis J, Ait-Si-Ali S. Sound of silence: the properties and functions of repressive Lys methyltransferases. Nat Rev Mol Cell Biol [Internet]. 2015 Aug;16(8):499–513. Shilatifard A. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem [Internet]. 2006;75:243–69. Hou H, Yu H. Structural insights into histone lysine demethylation. Curr Opin Struct Biol [Internet]. 2010 Dec;20(6):739–48. Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith OM, Misteli T. Regulation of alternative splicing by histone modifications. Science [Internet]. 2010 Feb 19;327(5968):996–1000. Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu XS, Ahringer J. Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet [Internet]. 2009 Mar;41(3):376–81. Bieberstein NI, Kozáková E, Huranová M, Thakur PK, Krchňáková Z, Krausová M, et al. TALE-directed local modulation of H3K9 methylation shapes exon recognition. Sci Rep [Internet]. 2016;6:29961. Di Lorenzo A, Bedford MT. Histone arginine methylation. FEBS Lett [Internet]. 2011 Jul 7;585(13):2024–31. Wesche J, Kühn S, Kessler BM, Salton M, Wolf A. Protein arginine methylation: a prominent modification and its demethylation. Cell Mol Life Sci [Internet]. 2017;74(18):3305–15. Carrozza MJ, Utley RT, Workman JL, Côté J. The diverse functions of histone acetyltransferase complexes. Trends Genet [Internet]. 2003 Jun;19(6):321–9. Rossetto D, Avvakumov N, Côté J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. Epigenetics [Internet]. 2012 Oct;7(10):1098–108. Cao J, Yan Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Front Oncol [Internet]. 2012;2:26. Cao R, Tsukada Y-I, Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell [Internet]. 2005 Dec 22;20(6):845–54. Minsky N, Shema E, Field Y, Schuster M, Segal E, Oren M. Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells. Nat Cell Biol [Internet]. 2008 Apr;10(4):483–8. Zhu B, Zheng Y, Pham A-D, Mandal SS, Erdjument-Bromage H, Tempst P, et al. Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol Cell [Internet]. 2005 Nov 23;20(4):601–11. Cubeñas-Potts C, Matunis MJ. SUMO: a multifaceted modifier of chromatin structure and function. Dev Cell [Internet]. 2013 Jan 14;24(1):1–12. Drag M, Salvesen GS. DeSUMOylating enzymes--SENPs. IUBMB Life [Internet]. 2008 Nov;60(11):734–42. Shin JA, Choi ES, Kim HS, Ho JCY, Watts FZ, Park SD, et al. SUMO modification is involved in the maintenance of heterochromatin stability in fission yeast. Mol Cell [Internet]. 2005 Sep 16;19(6):817–28. Uchimura Y, Ichimura T, Uwada J, Tachibana T, Sugahara S, Nakao M, et al. Involvement of SUMO modification in MBD1- and MCAF1-mediated heterochromatin formation. J Biol Chem [Internet]. 2006 Aug 11;281(32):23180–90. Wotton D, Pemberton LF, Merrill-Schools J. SUMO and Chromatin Remodeling. Adv Exp Med Biol [Internet]. 2017;963:35–50. Maison C, Almouzni G. HP1 and the dynamics of heterochromatin maintenance. Nat Rev Mol Cell Biol [Internet]. 2004 Apr;5(4):296–304. Fischle W, Tseng BS, Dormann HL, Ueberheide BM, Garcia BA, Shabanowitz J, et al. Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature [Internet]. 2005 Dec 22;438(7071):1116–22. Falkenberg KJ, Johnstone RW. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov [Internet]. 2014 Sep;13(9):673–91. Hyun K, Jeon J, Park K, Kim J. Writing, erasing and reading histone lysine methylations. Exp Mol Med [Internet]. 2017;49(4):e324. Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature [Internet]. 2006 May 18;441(7091):349–53. Mohn F, Weber M, Rebhan M, Roloff TC, Richter J, Stadler MB, et al. Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol Cell [Internet]. 2008 Jun 20;30(6):755–66. Brookes E, de Santiago I, Hebenstreit D, Morris KJ, Carroll T, Xie SQ, et al. Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. Cell Stem Cell [Internet]. 2012 Feb 3;10(2):157–70. Allis D. Epigenetics. Second. Cold Spring Harbor Laboratory Press; 2015. Dillon SC, Zhang X, Trievel RC, Cheng X. The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol [Internet]. 2005;6(8):227. Qian C, Zhou M-M. SET domain protein lysine methyltransferases: Structure, specificity and catalysis. Cell Mol Life Sci [Internet]. 2006 Dec;63(23):2755–63. Herz H-M, Garruss A, Shilatifard A. SET for life: biochemical activities and biological functions of SET domain-containing proteins. Trends Biochem Sci [Internet]. 2013 Dec;38(12):621–39. Matsumura Y, Nakaki R, Inagaki T, Yoshida A, Kano Y, Kimura H, et al. H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation. Mol Cell [Internet]. 2015 Nov 19;60(4):584–96. Nekrasov M, Wild B, Müller J. Nucleosome binding and histone methyltransferase activity of Drosophila PRC2. EMBO Rep [Internet]. 2005 Apr;6(4):348–53. Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature [Internet]. 2011 Jan 20;469(7330):343–9. Zhao J, Sun BK, Erwin JA, Song J-J, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science [Internet]. 2008 Oct 31;322(5902):750–6. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell [Internet]. 2007 Jun 29;129(7):1311–23. Collins RE, Northrop JP, Horton JR, Lee DY, Zhang X, Stallcup MR, et al. The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules. Nat Struct Mol Biol [Internet]. 2008 Mar;15(3):245–50. Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, et al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev [Internet]. 2002 Jul 15;16(14):1779–91. Rice JC, Briggs SD, Ueberheide B, Barber CM, Shabanowitz J, Hunt DF, et al. Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. Mol Cell [Internet]. 2003 Dec;12(6):1591–8. Happel N, Doenecke D. Histone H1 and its isoforms: contribution to chromatin structure and function. Gene [Internet]. 2009 Feb 15;431(1–2):1–12. Sampath SC, Marazzi I, Yap KL, Sampath SC, Krutchinsky AN, Mecklenbräuker I, et al. Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol Cell [Internet]. 2007 Aug 17;27(4):596–608. Tachibana M, Ueda J, Fukuda M, Takeda N, Ohta T, Iwanari H, et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev [Internet]. 2005 Apr 1;19(7):815–26. Feldman N, Gerson A, Fang J, Li E, Zhang Y, Shinkai Y, et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat Cell Biol [Internet]. 2006 Feb;8(2):188–94. Tschiersch B, Hofmann A, Krauss V, Dorn R, Korge G, Reuter G. The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes. EMBO J [Internet]. 1994 Aug 15;13(16):3822–31. Peters AH, O’Carroll D, Scherthan H, Mechtler K, Sauer S, Schöfer C, et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell [Internet]. 2001 Nov 2;107(3):323–37. Lehnertz B, Ueda Y, Derijck AAHA, Braunschweig U, Perez-Burgos L, Kubicek S, et al. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol [Internet]. 2003 Jul 15;13(14):1192–200. Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M, et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature [Internet]. 2000 Aug 10;406(6796):593–9. Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science [Internet]. 2001 Apr 6;292(5514):110–3. Nielsen SJ, Schneider R, Bauer UM, Bannister AJ, Morrison A, O’Carroll D, et al. Rb targets histone H3 methylation and HP1 to promoters. Nature [Internet]. 2001 Aug 2;412(6846):561–5. Blackburn ML, Chansky HA, Zielinska-Kwiatkowska A, Matsui Y, Yang L. Genomic structure and expression of the mouse ESET gene encoding an ERG-associated histone methyltransferase with a SET domain. Biochim Biophys Acta [Internet]. 2003 Oct 1;1629(1–3):8–14. Du Q, Luu P-L, Stirzaker C, Clark SJ. Methyl-CpG-binding domain proteins: readers of the epigenome. Epigenomics [Internet]. 2015;7(6):1051–73. Lohmann F, Loureiro J, Su H, Fang Q, Lei H, Lewis T, et al. KMT1E mediated H3K9 methylation is required for the maintenance of embryonic stem cells by repressing trophectoderm differentiation. Stem Cells [Internet]. 2010 Feb;28(2):201–12. Yuan P, Han J, Guo G, Orlov YL, Huss M, Loh Y-H, et al. Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells. Genes Dev [Internet]. 2009 Nov 1;23(21):2507–20. An J, Zhang X, Qin J, Wan Y, Hu Y, Liu T, et al. The histone methyltransferase ESET is required for the survival of spermatogonial stem/progenitor cells in mice. Cell Death Dis [Internet]. 2014;5:e1196. Tan S-L, Nishi M, Ohtsuka T, Matsui T, Takemoto K, Kamio-Miura A, et al. Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development. Development [Internet]. 2012 Oct;139(20):3806–16. Matsui T, Leung D, Miyashita H, Maksakova IA, Miyachi H, Kimura H, et al. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature [Internet]. 2010 Apr 8;464(7290):927–31. Kato M, Takemoto K, Shinkai Y. A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing. Nat Commun [Internet]. 2018 Apr 27;9(1):1683. Wu SC, Zhang Y. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol [Internet]. 2010 Sep;11(9):607–20. Ryan RF, Schultz DC, Ayyanathan K, Singh PB, Friedman JR, Fredericks WJ, et al. KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for Krüppel-associated box-zinc finger proteins in heterochromatin-mediated gene silencing. Mol Cell Biol [Internet]. 1999 Jun;19(6):4366–78. Iyengar S, Farnham PJ. KAP1 protein: an enigmatic master regulator of the genome. J Biol Chem [Internet]. 2011 Jul 29;286(30):26267–76. Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev [Internet]. 2002 Apr 15;16(8):919–32. Schultz DC, Friedman JR, Rauscher FJ. Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD. Genes Dev [Internet]. 2001 Feb 15;15(4):428–43. Van Duyne R, Easley R, Wu W, Berro R, Pedati C, Klase Z, et al. Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR. Retrovirology [Internet]. 2008 May 22;5:40. Cho S, Park JS, Kang Y-K. Regulated nuclear entry of over-expressed Setdb1. Genes Cells [Internet]. 2013 Aug;18(8):694–703. Otto A, Schmidt C, Luke G, Allen S, Valasek P, Muntoni F, et al. Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration. J Cell Sci [Internet]. 2008 Sep 1;121(Pt 17):2939–50. Maier VK, Feeney CM, Taylor JE, Creech AL, Qiao JW, Szanto A, et al. Functional Proteomic Analysis of Repressive Histone Methyltransferase Complexes Reveals ZNF518B as a G9A Regulator. Mol Cell Proteomics [Internet]. 2015 Jun;14(6):1435–46. Bian C, Chen Q, Yu X. The zinc finger proteins ZNF644 and WIZ regulate the G9a/GLP complex for gene repression. Elife [Internet]. 2015 Mar 19;4. Frietze S, O’Geen H, Blahnik KR, Jin VX, Farnham PJ. ZNF274 recruits the histone methyltransferase SETDB1 to the 3’ ends of ZNF genes. PLoS One [Internet]. 2010 Dec 8;5(12):e15082. Reed-Inderbitzin E, Moreno-Miralles I, Vanden-Eynden SK, Xie J, Lutterbach B, Durst-Goodwin KL, et al. RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription. Oncogene [Internet]. 2006 Sep 21;25(42):5777–86. Chakraborty S, Sinha KK, Senyuk V, Nucifora G. SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo. Oncogene [Internet]. 2003 Aug 14;22(34):5229–37. Mozzetta C, Pontis J, Fritsch L, Robin P, Portoso M, Proux C, et al. The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing. Mol Cell [Internet]. 2014 Jan 23;53(2):277–89. Fischle W, Franz H, Jacobs SA, Allis CD, Khorasanizadeh S. Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs. J Biol Chem [Internet]. 2008 Jul 11;283(28):19626–35. Mozzetta C, Pontis J, Ait-Si-Ali S. Functional Crosstalk Between Lysine Methyltransferases on Histone Substrates: The Case of G9A/GLP and Polycomb Repressive Complex 2. Antioxid Redox Signal [Internet]. 2015 Jun 1;22(16):1365–81. Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, et al. Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem [Internet]. 2003 Jun 27;278(26):24132–8. Wang H, An W, Cao R, Xia L, Erdjument-Bromage H, Chatton B, et al. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. Mol Cell [Internet]. 2003 Aug;12(2):475–87. Li H, Rauch T, Chen Z-X, Szabó PE, Riggs AD, Pfeifer GP. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem [Internet]. 2006 Jul 14;281(28):19489–500. Murayama A, Ohmori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, et al. Epigenetic control of rDNA loci in response to intracellular energy status. Cell [Internet]. 2008 May 16;133(4):627–39. Ameyar-Zazoua M, Rachez C, Souidi M, Robin P, Fritsch L, Young R, et al. Argonaute proteins couple chromatin silencing to alternative splicing. Nat Struct Mol Biol [Internet]. 2012 Oct;19(10):998–1004. Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, et al. Repression of p53 activity by Smyd2-mediated methylation. Nature [Internet]. 2006 Nov 30;444(7119):629–32. Hamamoto R, Saloura V, Nakamura Y. Critical roles of non-histone protein lysine methylation in human tumorigenesis. Nat Rev Cancer [Internet]. 2015 Feb;15(2):110–24. Zhang X, Tanaka K, Yan J, Li J, Peng D, Jiang Y, et al. Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation. Proc Natl Acad Sci U S A [Internet]. 2013 Oct 22;110(43):17284–9. Saddic LA, West LE, Aslanian A, Yates JR, Rubin SM, Gozani O, et al. Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem [Internet]. 2010 Nov 26;285(48):37733–40. Hamamoto R, Toyokawa G, Nakakido M, Ueda K, Nakamura Y. SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation. Cancer Lett [Internet]. 2014 Aug 28;351(1):126–33. Nishioka K, Chuikov S, Sarma K, Erdjument-Bromage H, Allis CD, Tempst P, et al. Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev [Internet]. 2002 Feb 15;16(4):479–89. Ivanov GS, Ivanova T, Kurash J, Ivanov A, Chuikov S, Gizatullin F, et al. Methylation-acetylation interplay activates p53 in response to DNA damage. Mol Cell Biol [Internet]. 2007 Oct;27(19):6756–69. Kurash JK, Lei H, Shen Q, Marston WL, Granda BW, Fan H, et al. Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo. Mol Cell [Internet]. 2008 Feb 15;29(3):392–400. Yang X-D, Huang B, Li M, Lamb A, Kelleher NL, Chen L-F. Negative regulation of NF-kappaB action by Set9-mediated lysine methylation of the RelA subunit. EMBO J [Internet]. 2009 Apr 22;28(8):1055–66. Ea C-K, Baltimore D. Regulation of NF-kappaB activity through lysine monomethylation of p65. Proc Natl Acad Sci U S A [Internet]. 2009 Nov 10;106(45):18972–7. Munro S, Khaire N, Inche A, Carr S, La Thangue NB. Lysine methylation regulates the pRb tumour suppressor protein. Oncogene [Internet]. 2010 Apr 22;29(16):2357–67. Wang D, Zhou J, Liu X, Lu D, Shen C, Du Y, et al. Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability. Proc Natl Acad Sci U S A [Internet]. 2013 Apr 2;110(14):5516–21. Mulligan P, Westbrook TF, Ottinger M, Pavlova N, Chang B, Macia E, et al. CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation. Mol Cell [Internet]. 2008 Dec 5;32(5):718–26. Huang J, Dorsey J, Chuikov S, Pérez-Burgos L, Zhang X, Jenuwein T, et al. G9a and Glp methylate lysine 373 in the tumor suppressor p53. J Biol Chem [Internet]. 2010 Mar 26;285(13):9636–41. Jacobs SA, Khorasanizadeh S. Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science [Internet]. 2002 Mar 15;295(5562):2080–3. Chin HG, Estève P-O, Pradhan M, Benner J, Patnaik D, Carey MF, et al. Automethylation of G9a and its implication in wider substrate specificity and HP1 binding. Nucleic Acids Res [Internet]. 2007;35(21):7313–23. Rathert P, Dhayalan A, Murakami M, Zhang X, Tamas R, Jurkowska R, et al. Protein lysine methyltransferase G9a acts on non-histone targets. Nat Chem Biol [Internet]. 2008 Jun;4(6):344–6. Ling BMT, Bharathy N, Chung T-K, Kok WK, Li S, Tan YH, et al. Lysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation. Proc Natl Acad Sci U S A [Internet]. 2012 Jan 17;109(3):841–6. Choi J, Jang H, Kim H, Lee J-H, Kim S-T, Cho E-J, et al. Modulation of lysine methylation in myocyte enhancer factor 2 during skeletal muscle cell differentiation. Nucleic Acids Res [Internet]. 2014 Jan;42(1):224–34. Leutz A, Pless O, Lappe M, Dittmar G, Kowenz-Leutz E. Crosstalk between phosphorylation and multi-site arginine/lysine methylation in C/EBPs. Transcription [Internet]. 2(1):3–8. Pless O, Kowenz-Leutz E, Knoblich M, Lausen J, Beyermann M, Walsh MJ, et al. G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta. J Biol Chem [Internet]. 2008 Sep 26;283(39):26357–63. Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, et al. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell [Internet]. 2011 Nov 11;147(4):773–88. Iglesias N, Currie MA, Jih G, Paulo JA, Siuti N, Kalocsay M, et al. Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability. Nature [Internet]. 2018 Jul 23. Piao L, Nakakido M, Suzuki T, Dohmae N, Nakamura Y, Hamamoto R. Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins. Oncotarget [Internet]. 2016 Apr 19;7(16):22846–56. Ryu H, Lee J, Hagerty SW, Soh BY, McAlpin SE, Cormier KA, et al. ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington’s disease. Proc Natl Acad Sci U S A [Internet]. 2006 Dec 12;103(50):19176–81. Lee J, Hwang YJ, Ryu H, Kowall NW, Ryu H. Nucleolar dysfunction in Huntington’s disease. Biochim Biophys Acta [Internet]. 2014 Jun;1842(6):785–90. Chen T, Li E. Structure and function of eukaryotic DNA methyltransferases. Curr Top Dev Biol [Internet]. 2004;60:55–89. Tirado-Magallanes R, Rebbani K, Lim R, Pradhan S, Benoukraf T. Whole genome DNA methylation: beyond genes silencing. Oncotarget [Internet]. 2017 Jan 17;8(3):5629–37. Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E, Jaenisch R, et al. Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development. Genes Dev [Internet]. 2008 Jun 15;22(12):1607–16. Ishida M, Moore GE. The role of imprinted genes in humans. Mol Aspects Med [Internet]. 34(4):826–40. Ito S, D’Alessio AC, Taranova O V, Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature [Internet]. 2010 Aug 26;466(7310):1129–33. Ruzov A, Tsenkina Y, Serio A, Dudnakova T, Fletcher J, Bai Y, et al. Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development. Cell Res [Internet]. 2011 Sep;21(9):1332–42. Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA, et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature [Internet]. 2011 May 19;473(7347):398–402. Leung DC, Dong KB, Maksakova IA, Goyal P, Appanah R, Lee S, et al. Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing. Proc Natl Acad Sci U S A [Internet]. 2011 Apr 5;108(14):5718–23. Dong KB, Maksakova IA, Mohn F, Leung D, Appanah R, Lee S, et al. DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity. EMBO J [Internet]. 2008 Oct 22;27(20):2691–701. Epsztejn-Litman S, Feldman N, Abu-Remaileh M, Shufaro Y, Gerson A, Ueda J, et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat Struct Mol Biol [Internet]. 2008 Nov;15(11):1176–83. Arita K, Isogai S, Oda T, Unoki M, Sugita K, Sekiyama N, et al. Recognition of modification status on a histone H3 tail by linked histone reader modules of the epigenetic regulator UHRF1. Proc Natl Acad Sci U S A [Internet]. 2012 Aug 7;109(32):12950–5. Rothbart SB, Dickson BM, Ong MS, Krajewski K, Houliston S, Kireev DB, et al. Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation. Genes Dev [Internet]. 2013 Jun 1;27(11):1288–98. Girardot M, Cavaillé J, Feil R. Small regulatory RNAs controlled by genomic imprinting and their contribution to human disease. Epigenetics [Internet]. 2012 Dec 1;7(12):1341–8. Barlow DP. Genomic imprinting: a mammalian epigenetic discovery model. Annu Rev Genet [Internet]. 2011;45:379–403. Sanli I, Feil R. Chromatin mechanisms in the developmental control of imprinted gene expression. Int J Biochem Cell Biol [Internet]. 2015 Oct;67:139–47. Barlow DP, Bartolomei MS. Genomic imprinting in mammals. Cold Spring Harb Perspect Biol [Internet]. 2014 Feb 1;6(2). Kota SK, Feil R. Epigenetic transitions in germ cell development and meiosis. Dev Cell [Internet]. 2010 Nov 16;19(5):675–86. Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, et al. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev Cell [Internet]. 2008 Oct;15(4):547–57. Reese KJ, Lin S, Verona RI, Schultz RM, Bartolomei MS. Maintenance of paternal methylation and repression of the imprinted H19 gene requires MBD3. PLoS Genet [Internet]. 2007 Aug;3(8):e137. Ma P, Lin S, Bartolomei MS, Schultz RM. Metastasis tumor antigen 2 (MTA2) is involved in proper imprinted expression of H19 and Peg3 during mouse preimplantation development. Biol Reprod [Internet]. 2010 Dec;83(6):1027–35. Wu M-Y, Tsai T-F, Beaudet AL. Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain. Genes Dev [Internet]. 2006 Oct 15;20(20):2859–70. Pauler FM, Barlow DP, Hudson QJ. Mechanisms of long range silencing by imprinted macro non-coding RNAs. Curr Opin Genet Dev [Internet]. 2012 Jun;22(3):283–9. Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell [Internet]. 2008 Oct 24;32(2):232–46. Li Q, Su Z, Xu X, Liu G, Song X, Wang R, et al. AS1DHRS4, a head-to-head natural antisense transcript, silences the DHRS4 gene cluster in cis and trans. Proc Natl Acad Sci U S A [Internet]. 2012 Aug 28;109(35):14110–5. Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, et al. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science [Internet]. 2008 Dec 12;322(5908):1717–20. Kota SK, Llères D, Bouschet T, Hirasawa R, Marchand A, Begon-Pescia C, et al. ICR noncoding RNA expression controls imprinting and DNA replication at the Dlk1-Dio3 domain. Dev Cell [Internet]. 2014 Oct 13;31(1):19–33. Deininger PL, Batzer MA. Mammalian retroelements. Genome Res [Internet]. 2002 Oct;12(10):1455–65. Faulkner GJ, Carninci P. Altruistic functions for selfish DNA. Cell Cycle [Internet]. 2009 Sep 15;8(18):2895–900. Slotkin RK, Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet [Internet]. 2007 Apr;8(4):272–85. Böhne A, Brunet F, Galiana-Arnoux D, Schultheis C, Volff J-N. Transposable elements as drivers of genomic and biological diversity in vertebrates. Chromosome Res [Internet]. 2008;16(1):203–15. Cordaux R, Batzer MA. The impact of retrotransposons on human genome evolution. Nat Rev Genet [Internet]. 2009 Oct;10(10):691–703. Levin HL, Moran J V. Dynamic interactions between transposable elements and their hosts. Nat Rev Genet [Internet]. 2011 Aug 18;12(9):615–27. Garcia-Perez JL, Widmann TJ, Adams IR. The impact of transposable elements on mammalian development. Development [Internet]. 2016;143(22):4101–14. Mager DL, Stoye JP. Mammalian Endogenous Retroviruses. Microbiol Spectr [Internet]. 2015 Feb;3(1):MDNA3-0009-2014. Boeke J, Stoye J. Retrotransposons, Endogenous Retroviruses, and the Evolution of Retroelements [Internet]. Retroviruses. 1997. Ribet D, Harper F, Dupressoir A, Dewannieux M, Pierron G, Heidmann T. An infectious progenitor for the murine IAP retrotransposon: emergence of an intracellular genetic parasite from an ancient retrovirus. Genome Res [Internet]. 2008 Apr;18(4):597–609. Ribet D, Harper F, Dewannieux M, Pierron G, Heidmann T. Murine MusD retrotransposon: structure and molecular evolution of an “intracellularized” retrovirus. J Virol [Internet]. 2007 Feb;81(4):1888–98. Friedli M, Trono D. The developmental control of transposable elements and the evolution of higher species. Annu Rev Cell Dev Biol [Internet]. 2015;31:429–51. Marchi E, Kanapin A, Magiorkinis G, Belshaw R. Unfixed endogenous retroviral insertions in the human population. J Virol [Internet]. 2014 Sep 1;88(17):9529–37. Kuff EL, Lueders KK. The intracisternal A-particle gene family: structure and functional aspects. Adv Cancer Res [Internet]. 1988;51:183–276. Ribet D, Dewannieux M, Heidmann T. An active murine transposon family pair: retrotransposition of “master” MusD copies and ETn trans-mobilization. Genome Res [Internet]. 2004 Nov;14(11):2261–7. Peaston AE, Evsikov A V, Graber JH, de Vries WN, Holbrook AE, Solter D, et al. Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell [Internet]. 2004 Oct;7(4):597–606. Medstrand P, van de Lagemaat LN, Mager DL. Retroelement distributions in the human genome: variations associated with age and proximity to genes. Genome Res [Internet]. 2002 Oct;12(10):1483–95. Beck CR, Collier P, Macfarlane C, Malig M, Kidd JM, Eichler EE, et al. LINE-1 retrotransposition activity in human genomes. Cell [Internet]. 2010 Jun 25;141(7):1159–70. Elbarbary RA, Lucas BA, Maquat LE. Retrotransposons as regulators of gene expression. Science [Internet]. 2016 Feb 12;351(6274):aac7247. Luan DD, Eickbush TH. RNA template requirements for target DNA-primed reverse transcription by the R2 retrotransposable element. Mol Cell Biol [Internet]. 1995 Jul;15(7):3882–91. Leung DC, Lorincz MC. Silencing of endogenous retroviruses: when and why do histone marks predominate? Trends Biochem Sci [Internet]. 2012 Apr;37(4):127–33. Rowe HM, Trono D. Dynamic control of endogenous retroviruses during development. Virology [Internet]. 2011 Mar 15;411(2):273–87. Collins PL, Kyle KE, Egawa T, Shinkai Y, Oltz EM. The histone methyltransferase SETDB1 represses endogenous and exogenous retroviruses in B lymphocytes. Proc Natl Acad Sci U S A [Internet]. 2015 Jul 7;112(27):8367–72. Liu S, Brind’Amour J, Karimi MM, Shirane K, Bogutz A, Lefebvre L, et al. Setdb1 is required for germline development and silencing of H3K9me3-marked endogenous retroviruses in primordial germ cells. Genes Dev [Internet]. 2014 Sep 15;28(18):2041–55. Rowe HM, Friedli M, Offner S, Verp S, Mesnard D, Marquis J, et al. De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET. Development [Internet]. 2013 Feb 1;140(3):519–29. Leung D, Du T, Wagner U, Xie W, Lee AY, Goyal P, et al. Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1. Proc Natl Acad Sci U S A [Internet]. 2014 May 6;111(18):6690–5. Castro-Diaz N, Ecco G, Coluccio A, Kapopoulou A, Yazdanpanah B, Friedli M, et al. Evolutionally dynamic L1 regulation in embryonic stem cells. Genes Dev [Internet]. 2014 Jul 1;28(13):1397–409. Turelli P, Castro-Diaz N, Marzetta F, Kapopoulou A, Raclot C, Duc J, et al. Interplay of TRIM28 and DNA methylation in controlling human endogenous retroelements. Genome Res [Internet]. 2014 Aug;24(8):1260–70. Maksakova IA, Thompson PJ, Goyal P, Jones SJ, Singh PB, Karimi MM, et al. Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells. Epigenetics Chromatin [Internet]. 2013 Jun 4;6(1):15. Chiba T, Saito T, Yuki K, Zen Y, Koide S, Kanogawa N, et al. Histone lysine methyltransferase SUV39H1 is a potent target for epigenetic therapy of hepatocellular carcinoma. Int J cancer [Internet]. 2015 Jan 15;136(2):289–98. Khanal P, Kim G, Lim S-C, Yun H-J, Lee KY, Choi H-K, et al. Prolyl isomerase Pin1 negatively regulates the stability of SUV39H1 to promote tumorigenesis in breast cancer. FASEB J [Internet]. 2013 Nov;27(11):4606–18. Dworkin AM, Huang TH-M, Toland AE. Epigenetic alterations in the breast: Implications for breast cancer detection, prognosis and treatment. Semin Cancer Biol [Internet]. 2009 Jun;19(3):165–71. Tan J, Yang X, Zhuang L, Jiang X, Chen W, Lee PL, et al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev [Internet]. 2007 May 1;21(9):1050–63. Casciello F, Windloch K, Gannon F, Lee JS. Functional Role of G9a Histone Methyltransferase in Cancer. Front Immunol [Internet]. 2015;6:487. Zhang H, Cai K, Wang J, Wang X, Cheng K, Shi F, et al. MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway. Stem Cells [Internet]. 2014 Nov;32(11):2858–68. Regina C, Compagnone M, Peschiaroli A, Lena A, Annicchiarico-Petruzzelli M, Piro MC, et al. Setdb1, a novel interactor of ΔNp63, is involved in breast tumorigenesis. Oncotarget [Internet]. Guo A, Gu H, Zhou J, Mulhern D, Wang Y, Lee KA, et al. Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol Cell Proteomics [Internet]. 2014 Jan;13(1):372–87. Karimi MM, Goyal P, Maksakova IA, Bilenky M, Leung D, Tang JX, et al. DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs. Cell Stem Cell [Internet]. 2011 Jun 3;8(6):676–87. Xu S, Grullon S, Ge K, Peng W. Spatial clustering for identification of ChIP-enriched regions (SICER) to map regions of histone methylation patterns in embryonic stem cells. Methods Mol Biol [Internet]. 2014;1150:97–111. Peters AHFM, Kubicek S, Mechtler K, O’Sullivan RJ, Derijck AAHA, Perez-Burgos L, et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell [Internet]. 2003 Dec;12(6):1577–89. Walter M, Teissandier A, Pérez-Palacios R, Bourc’his D. An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. Elife [Internet]. 2016 Jan 27;5. Kourmouli N, Sun Y, van der Sar S, Singh PB, Brown JP. Epigenetic regulation of mammalian pericentric heterochromatin in vivo by HP1. Biochem Biophys Res Commun [Internet]. 2005 Nov 25;337(3):901–7. Deribe YL, Pawson T, Dikic I. Post-translational modifications in signal integration. Nat Struct Mol Biol [Internet]. 2010 Jun;17(6):666–72. AMBLER RP, REES MW. Epsilon-N-Methyl-lysine in bacterial flagellar protein. Nature [Internet]. 1959 Jul 4;184:56–7. Murn J, Shi Y. The winding path of protein methylation research: milestones and new frontiers. Nat Rev Mol Cell Biol [Internet]. 2017;18(8):517–27. Fischle W, Wang Y, Allis CD. Binary switches and modification cassettes in histone biology and beyond. Nature [Internet]. 2003 Oct 2;425(6957):475–9. Qin R, Cao S, Lyu T, Qi C, Zhang W, Wang Y. CDYL Deficiency Disrupts Neuronal Migration and Increases Susceptibility to Epilepsy. Cell Rep [Internet]. 2017;18(2):380–90. Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev [Internet]. 2003 Aug 1;17(15):1870–81. Thompson PJ, Macfarlan TS, Lorincz MC. Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire. Mol Cell [Internet]. 2016;62(5):766–76. Hutnick LK, Huang X, Loo T-C, Ma Z, Fan G. Repression of retrotransposal elements in mouse embryonic stem cells is primarily mediated by a DNA methylation-independent mechanism. J Biol Chem [Internet]. 2010 Jul 2;285(27):21082–91. Seisenberger S, Peat JR, Reik W. Conceptual links between DNA methylation reprogramming in the early embryo and primordial germ cells. Curr Opin Cell Biol [Internet]. 2013 Jun;25(3):281–8. Leeb M, Pasini D, Novatchkova M, Jaritz M, Helin K, Wutz A. Polycomb complexes act redundantly to repress genomic repeats and genes. Genes Dev [Internet]. 2010 Feb 1;24(3):265–76. Wolf G, Macfarlan TS. Revealing the complexity of retroviral repression. Cell [Internet]. 2015 Sep 24;163(1):30–2. Maksakova IA, Goyal P, Bullwinkel J, Brown JP, Bilenky M, Mager DL, et al. H3K9me3-binding proteins are dispensable for SETDB1/H3K9me3-dependent retroviral silencing. Epigenetics Chromatin [Internet]. 2011 Jul 20;4(1):12. Jamieson K, Wiles ET, McNaught KJ, Sidoli S, Leggett N, Shao Y, et al. Loss of HP1 causes depletion of H3K27me3 from facultative heterochromatin and gain of H3K27me2 at constitutive heterochromatin. Genome Res [Internet]. 2016 Jan;26(1):97–107. Zuo X, Sheng J, Lau H-T, McDonald CM, Andrade M, Cullen DE, et al. Zinc finger protein ZFP57 requires its co-factor to recruit DNA methyltransferases and maintains DNA methylation imprint in embryonic stem cells via its transcriptional repression domain. J Biol Chem [Internet]. 2012 Jan 13;287(3):2107–18. Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, et al. The transcriptional and epigenomic foundations of ground state pluripotency. Cell [Internet]. 2012 Apr 27;149(3):590–604. Pathak R, Feil R. Environmental effects on chromatin repression at imprinted genes and endogenous retroviruses. Curr Opin Chem Biol [Internet]. 2018 May 23;45:139–47. Zhang Y, Yang X, Gui B, Xie G, Zhang D, Shang Y, et al. Corepressor protein CDYL functions as a molecular bridge between polycomb repressor complex 2 and repressive chromatin mark trimethylated histone lysine 27. J Biol Chem [Internet]. 2011 Dec 9;286(49):42414–25. Liu Y, Liu S, Yuan S, Yu H, Zhang Y, Yang X, et al. Chromodomain protein CDYL is required for transmission/restoration of repressive histone marks. J Mol Cell Biol [Internet]. 2017 Jun 1;9(3):178–94. Matouk IJ, Halle D, Gilon M, Hochberg A. The non-coding RNAs of the H19-IGF2 imprinted loci: a focus on biological roles and therapeutic potential in Lung Cancer. J Transl Med [Internet]. 2015 Apr 9;13:113. Beyer S, Pontis J, Schirwis E, Battisti V, Rudolf A, Le Grand F, et al. Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation. Cell Discov [Internet]. 2016;2:16037. Mercatelli N, Beldiman C, Brouard T, Nairismägi M, Kratassiouk G, Largitte L, et al. Mir-205 modulates acinar size and morphology of transformed breast epithelial cells. OncomiRs. 2012;2–9. Jiang Y, Loh Y-HE, Rajarajan P, Hirayama T, Liao W, Kassim BS, et al. The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain. Nat Genet [Internet]. 2017 Aug;49(8):1239–50. Walker CJ, Miranda MA, O’Hern MJ, McElroy JP, Coombes KR, Bundschuh R, et al. Patterns of CTCF and ZFHX3 Mutation and Associated Outcomes in Endometrial Cancer. J Natl Cancer Inst [Internet]. 2015 Nov;107(11). Goke J, Ng HH. CTRL-INSERT: retrotransposons and their contribution to regulation and innovation of the transcriptome. EMBO Rep [Internet]. 2016;17(8):1131–44.
dc.source.instname.spa.fl_str_mv	instname:Universidad del Rosario
dc.source.reponame.spa.fl_str_mv	reponame:Repositorio Institucional EdocUR
bitstream.url.fl_str_mv	https://repository.urosario.edu.co/bitstreams/ac1f3e8d-beea-4c1a-855a-407962b88251/download https://repository.urosario.edu.co/bitstreams/c2df54b2-52dd-4a8a-bb7c-7b5d7f30abac/download https://repository.urosario.edu.co/bitstreams/0804d990-ef8f-4401-959d-d421601bfe47/download https://repository.urosario.edu.co/bitstreams/2cf7b16e-416b-4f31-8b7c-b340daf050c4/download https://repository.urosario.edu.co/bitstreams/0457879a-1e90-4894-bcf9-2c27c34cbf16/download https://repository.urosario.edu.co/bitstreams/bf18ae70-8b89-4449-a24a-9db1cb01b204/download https://repository.urosario.edu.co/bitstreams/31395790-1ace-4a78-a5d9-61b52b46df4b/download https://repository.urosario.edu.co/bitstreams/6865da18-0aff-4254-9cf0-e5d697634451/download
bitstream.checksum.fl_str_mv	97b4923567f4fa36741cfce8c3c808f2 9e32a0b8bca41d20d5cd480f11fb83b2 9f5eb859bd5c30bc88515135ce7ba417 fab9d9ed61d64f6ac005dee3306ae77e 5a9c175324992f7657dad808f08f76da 14c32781c6f946f823ab944eb95bdc94 2537fb873b6bdb09b91f39da0580234a 42fd8a3d0de1a219dcef00f75e3e68ed
bitstream.checksumAlgorithm.fl_str_mv	MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5
repository.name.fl_str_mv	Repositorio institucional EdocUR
repository.mail.fl_str_mv	edocur@urosario.edu.co
_version_	1814167620896686080
spelling	Ait-Si-Ali, Slimane4e6c4eaa-cb61-473e-aefe-889f587ee4cd600Ramírez Clavijo, Sandra Rocío51866251600Cruz Tapias, Paola AndreaDoctor en Ciencias BiomédicasFull time03192832-4b9c-452c-ad2b-3b0505fa248f6002019-06-04T20:50:36Z2019-06-04T20:50:36Z2018-09-212018La tri-metilación de la lisina 9 de la histona 3 (H3K9me3) es una modificación epigenética requerida para la formación y el mantenimiento de la heterocromatina, la estabilidad genómica y el silenciamiento de elementos transposables en células madre embrionarias (CMEs). SETDB1 es una metiltransferasa específica de la lisina 9 de la histona 3 crucial durante el desarrollo de los mamíferos debido a que regula la pluripotencia de las CMEs en el embrión. Los resultados de este trabajo sugieren que SETDB1 lleva a cabo un proceso de auto-metilación que es requerido para el mantenimiento de la pluripotencia, el crecimiento y la viabilidad de las CMEs murinas. Adicionalmente, análisis de transcriptoma completo (RNA-seq) mostraron que la integridad de las dos lisinas auto-metiladas es requerida para el silenciamiento tanto de genes codificantes como de elementos transposables. De hecho, análisis de ChIP-seq revelaron que una deficiencia en la auto-metilación conlleva a una disminución en el establecimiento de H3K9me3 en loci blanco. Nuestros resultados sugieren que la auto-metilación de SETDB1 es un pre-requisito para la trans-metilación por SUV39H1. Este mecanismo podría regular no solamente la interacción física entre SETDB1 y SUV39H1 (vía el cromodominio de SUV39H1), sino también la cooperación para el establecimiento y el mantenimiento de la heterocromatina y el silenciamiento de los elementos transposables. Por todo lo anterior, los resultados de este trabajo revelan un nuevo mecanismo que regula las funciones de SETDB1, el cual es crucial para la identidad y el mantenimiento de las CMEs.Histone H3 lysine 9 trimethylation (H3K9me3) is a key epigenetic modification required for heterochromatin formation and maintenance, genome stability and silencing of transposable elements in embryonic stems cells (ESCs). The H3K9-specific methyltransferase (KMT) SETDB1 is vital for mammalian development as it regulates ESCs pluripotency in the early embryo. Here we unravel that SETDB1 undergoes automethylation on two lysines, embedded within its catalytic domain, both in vitro and in cells. Importantly, SETDB1 automethylation is required for mouse ESCs stemness, growth and viability. Hence, transcriptome-wide analyses (RNA-seq) show that the integrity of the two SETDB1 automethylated lysines is required for both coding genes and transposable elements silencing in mESCs. Indeed, our analyses of ChIP-seq show that automethylation-deficient SETDB1 expression leads to a lack of H3K9me3 establishment at target loci. Interestingly, our results point to a model in which SETDB1 auto-methylation paves the path to a subsequent trans-methylation by SUV39H1. This mechanism could regulate not only the SETDB1/SUV39H1 physical interaction (via the SUV39H1 chromodomain), but also cooperation in the establishment and maintenance of both heterochromatin blocks (large domains) and transposable elements silencing. Taken together, my findings uncover a novel mechanism regulating SETDB1 KMT key functions that are key in embryonic stems cells identity maintenance.2021-06-05 01:01:01: Script de automatizacion de embargos. info:eu-repo/date/embargoEnd/2021-06-04application/pdfhttps://doi.org/10.48713/10336_19828 http://repository.urosario.edu.co/handle/10336/19828engUniversidad del RosarioFacultad de Ciencias Naturales y MatemáticasDoctorado en Ciencias BiomédicasAtribución-NoComercial-SinDerivadas 2.5 ColombiaAbierto (Texto Completo)EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DEL ROSARIO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. -------------------------------------- POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DEL ROSARIO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. Para el correcto ejercicio de mi derecho de habeas data cuento con la cuenta de correo habeasdata@urosario.edu.co, donde previa identificación podré solicitar la consulta, corrección y supresión de mis datos.http://creativecommons.org/licenses/by-nc-nd/2.5/co/http://purl.org/coar/access_right/c_abf2Fritsch L, Robin P, Mathieu JRR, Souidi M, Hinaux H, Rougeulle C, et al. A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Mol Cell [Internet]. 2010 Jan 15;37(1):46–56.Ishimoto K, Kawamata N, Uchihara Y, Okubo M, Fujimoto R, Gotoh E, et al. Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity. PLoS One [Internet]. 2016;11(10):e0165766.Yeap L-S, Hayashi K, Surani MA. ERG-associated protein with SET domain (ESET)-Oct4 interaction regulates pluripotency and represses the trophectoderm lineage. Epigenetics Chromatin [Internet]. 2009;2(1):12.Bilodeau S, Kagey MH, Frampton GM, Rahl PB, Young RA. SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state. Genes Dev [Internet]. 2009 Nov 1;23(21):2484–9.Dodge JE, Kang Y-K, Beppu H, Lei H, Li E. Histone H3-K9 methyltransferase ESET is essential for early development. Mol Cell Biol [Internet]. 2004 Mar;24(6):2478–86.Binda O, LeRoy G, Bua DJ, Garcia BA, Gozani O, Richard S. Trimethylation of histone H3 lysine 4 impairs methylation of histone H3 lysine 9: regulation of lysine methyltransferases by physical interaction with their substrates. Epigenetics [Internet]. 5(8):767–75.Fei Q, Shang K, Zhang J, Chuai S, Kong D, Zhou T, et al. Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53. Nat Commun [Internet]. 2015;6:8651.Hwang YJ, Han D, Kim KY, Min S-J, Kowall NW, Yang L, et al. ESET methylates UBF at K232/254 and regulates nucleolar heterochromatin plasticity and rDNA transcription. Nucleic Acids Res [Internet]. 2014 Feb;42(3):1628–43.Loyola A, Tagami H, Bonaldi T, Roche D, Quivy JP, Imhof A, et al. The HP1alpha-CAF1-SetDB1-containing complex provides H3K9me1 for Suv39-mediated K9me3 in pericentric heterochromatin. EMBO Rep [Internet]. 2009 Jul;10(7):769–75.Towbin BD, González-Aguilera C, Sack R, Gaidatzis D, Kalck V, Meister P, et al. Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell [Internet]. 2012 Aug 31;150(5):934–47.Bulut-Karslioglu A, De La Rosa-Velázquez IA, Ramirez F, Barenboim M, Onishi-Seebacher M, Arand J, et al. Suv39h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells. Mol Cell [Internet]. 2014 Jul 17;55(2):277–90.Baylin SB, Jones PA. A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer [Internet]. 2011 Oct;11(10):726–34.Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet [Internet]. 2012 Apr 3;13(5):343–57.Ding J, Li T, Wang X, Zhao E, Choi J-H, Yang L, et al. The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. Cell Metab [Internet]. 2013 Dec 3;18(6):896–907.Ceol CJ, Houvras Y, Jane-Valbuena J, Bilodeau S, Orlando DA, Battisti V, et al. The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature [Internet]. 2011 Mar 24;471(7339):513–7.Rodriguez-Paredes M, Martinez de Paz A, Simó-Riudalbas L, Sayols S, Moutinho C, Moran S, et al. Gene amplification of the histone methyltransferase SETDB1 contributes to human lung tumorigenesis. Oncogene [Internet]. 2014 May 22;33(21):2807–13.Liu L, Kimball S, Liu H, Holowatyj A, Yang Z-Q. Genetic alterations of histone lysine methyltransferases and their significance in breast cancer. Oncotarget [Internet]. 2015 Feb 10;6(4):2466–82.Burns KH, Boeke JD. Human transposon tectonics. Cell [Internet]. 2012 May 11;149(4):740–52.Waddington CH. The epigenotype. Endeavour. 1942;1:18.Baxter E, Windloch K, Gannon F, Lee JS. Epigenetic regulation in cancer progression. Cell Biosci [Internet]. 2014;4:45.Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature [Internet]. 2004 May 27;429(6990):457–63.Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res [Internet]. 2011 Mar;21(3):381–95.Saksouk N, Simboeck E, Déjardin J. Constitutive heterochromatin formation and transcription in mammals. Epigenetics Chromatin [Internet]. 2015;8:3.Grewal SIS, Jia S. Heterochromatin revisited. Nat Rev Genet [Internet]. 2007 Jan;8(1):35–46.Nishibuchi G, Déjardin J. The molecular basis of the organization of repetitive DNA-containing constitutive heterochromatin in mammals. Chromosome Res [Internet]. 2017 Mar;25(1):77–87.Wang J, Jia ST, Jia S. New Insights into the Regulation of Heterochromatin. Trends Genet [Internet]. 2016;32(5):284–94.Martin C, Zhang Y. The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol [Internet]. 2005 Nov;6(11):838–49.Jenuwein T, Allis CD. Translating the histone code. Science [Internet]. 2001 Aug 10;293(5532):1074–80.Ronner P. Netter’s Essential Biochemistry. First edit. Elsevier Health Sciences; 2016. 43 p.Felsenfeld G, Groudine M. Controlling the double helix. Nature [Internet]. 2003 Jan 23;421(6921):448–53.Bhaumik SR, Smith E, Shilatifard A. Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol [Internet]. 2007 Nov;14(11):1008–16.Huynh JL, Casaccia P. Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol [Internet]. 2013 Feb;12(2):195–206.Mozzetta C, Boyarchuk E, Pontis J, Ait-Si-Ali S. Sound of silence: the properties and functions of repressive Lys methyltransferases. Nat Rev Mol Cell Biol [Internet]. 2015 Aug;16(8):499–513.Shilatifard A. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem [Internet]. 2006;75:243–69.Hou H, Yu H. Structural insights into histone lysine demethylation. Curr Opin Struct Biol [Internet]. 2010 Dec;20(6):739–48.Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith OM, Misteli T. Regulation of alternative splicing by histone modifications. Science [Internet]. 2010 Feb 19;327(5968):996–1000.Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu XS, Ahringer J. Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet [Internet]. 2009 Mar;41(3):376–81.Bieberstein NI, Kozáková E, Huranová M, Thakur PK, Krchňáková Z, Krausová M, et al. TALE-directed local modulation of H3K9 methylation shapes exon recognition. Sci Rep [Internet]. 2016;6:29961.Di Lorenzo A, Bedford MT. Histone arginine methylation. FEBS Lett [Internet]. 2011 Jul 7;585(13):2024–31.Wesche J, Kühn S, Kessler BM, Salton M, Wolf A. Protein arginine methylation: a prominent modification and its demethylation. Cell Mol Life Sci [Internet]. 2017;74(18):3305–15.Carrozza MJ, Utley RT, Workman JL, Côté J. The diverse functions of histone acetyltransferase complexes. Trends Genet [Internet]. 2003 Jun;19(6):321–9.Rossetto D, Avvakumov N, Côté J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. Epigenetics [Internet]. 2012 Oct;7(10):1098–108.Cao J, Yan Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Front Oncol [Internet]. 2012;2:26.Cao R, Tsukada Y-I, Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell [Internet]. 2005 Dec 22;20(6):845–54.Minsky N, Shema E, Field Y, Schuster M, Segal E, Oren M. Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells. Nat Cell Biol [Internet]. 2008 Apr;10(4):483–8.Zhu B, Zheng Y, Pham A-D, Mandal SS, Erdjument-Bromage H, Tempst P, et al. Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol Cell [Internet]. 2005 Nov 23;20(4):601–11.Cubeñas-Potts C, Matunis MJ. SUMO: a multifaceted modifier of chromatin structure and function. Dev Cell [Internet]. 2013 Jan 14;24(1):1–12.Drag M, Salvesen GS. DeSUMOylating enzymes--SENPs. IUBMB Life [Internet]. 2008 Nov;60(11):734–42.Shin JA, Choi ES, Kim HS, Ho JCY, Watts FZ, Park SD, et al. SUMO modification is involved in the maintenance of heterochromatin stability in fission yeast. Mol Cell [Internet]. 2005 Sep 16;19(6):817–28.Uchimura Y, Ichimura T, Uwada J, Tachibana T, Sugahara S, Nakao M, et al. Involvement of SUMO modification in MBD1- and MCAF1-mediated heterochromatin formation. J Biol Chem [Internet]. 2006 Aug 11;281(32):23180–90.Wotton D, Pemberton LF, Merrill-Schools J. SUMO and Chromatin Remodeling. Adv Exp Med Biol [Internet]. 2017;963:35–50.Maison C, Almouzni G. HP1 and the dynamics of heterochromatin maintenance. Nat Rev Mol Cell Biol [Internet]. 2004 Apr;5(4):296–304.Fischle W, Tseng BS, Dormann HL, Ueberheide BM, Garcia BA, Shabanowitz J, et al. Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature [Internet]. 2005 Dec 22;438(7071):1116–22.Falkenberg KJ, Johnstone RW. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov [Internet]. 2014 Sep;13(9):673–91.Hyun K, Jeon J, Park K, Kim J. Writing, erasing and reading histone lysine methylations. Exp Mol Med [Internet]. 2017;49(4):e324.Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature [Internet]. 2006 May 18;441(7091):349–53.Mohn F, Weber M, Rebhan M, Roloff TC, Richter J, Stadler MB, et al. Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol Cell [Internet]. 2008 Jun 20;30(6):755–66.Brookes E, de Santiago I, Hebenstreit D, Morris KJ, Carroll T, Xie SQ, et al. Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. Cell Stem Cell [Internet]. 2012 Feb 3;10(2):157–70.Allis D. Epigenetics. Second. Cold Spring Harbor Laboratory Press; 2015.Dillon SC, Zhang X, Trievel RC, Cheng X. The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol [Internet]. 2005;6(8):227.Qian C, Zhou M-M. SET domain protein lysine methyltransferases: Structure, specificity and catalysis. Cell Mol Life Sci [Internet]. 2006 Dec;63(23):2755–63.Herz H-M, Garruss A, Shilatifard A. SET for life: biochemical activities and biological functions of SET domain-containing proteins. Trends Biochem Sci [Internet]. 2013 Dec;38(12):621–39.Matsumura Y, Nakaki R, Inagaki T, Yoshida A, Kano Y, Kimura H, et al. H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation. Mol Cell [Internet]. 2015 Nov 19;60(4):584–96.Nekrasov M, Wild B, Müller J. Nucleosome binding and histone methyltransferase activity of Drosophila PRC2. EMBO Rep [Internet]. 2005 Apr;6(4):348–53.Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature [Internet]. 2011 Jan 20;469(7330):343–9.Zhao J, Sun BK, Erwin JA, Song J-J, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science [Internet]. 2008 Oct 31;322(5902):750–6.Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell [Internet]. 2007 Jun 29;129(7):1311–23.Collins RE, Northrop JP, Horton JR, Lee DY, Zhang X, Stallcup MR, et al. The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules. Nat Struct Mol Biol [Internet]. 2008 Mar;15(3):245–50.Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, et al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev [Internet]. 2002 Jul 15;16(14):1779–91.Rice JC, Briggs SD, Ueberheide B, Barber CM, Shabanowitz J, Hunt DF, et al. Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. Mol Cell [Internet]. 2003 Dec;12(6):1591–8.Happel N, Doenecke D. Histone H1 and its isoforms: contribution to chromatin structure and function. Gene [Internet]. 2009 Feb 15;431(1–2):1–12.Sampath SC, Marazzi I, Yap KL, Sampath SC, Krutchinsky AN, Mecklenbräuker I, et al. Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol Cell [Internet]. 2007 Aug 17;27(4):596–608.Tachibana M, Ueda J, Fukuda M, Takeda N, Ohta T, Iwanari H, et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev [Internet]. 2005 Apr 1;19(7):815–26.Feldman N, Gerson A, Fang J, Li E, Zhang Y, Shinkai Y, et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat Cell Biol [Internet]. 2006 Feb;8(2):188–94.Tschiersch B, Hofmann A, Krauss V, Dorn R, Korge G, Reuter G. The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes. EMBO J [Internet]. 1994 Aug 15;13(16):3822–31.Peters AH, O’Carroll D, Scherthan H, Mechtler K, Sauer S, Schöfer C, et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell [Internet]. 2001 Nov 2;107(3):323–37.Lehnertz B, Ueda Y, Derijck AAHA, Braunschweig U, Perez-Burgos L, Kubicek S, et al. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol [Internet]. 2003 Jul 15;13(14):1192–200.Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M, et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature [Internet]. 2000 Aug 10;406(6796):593–9.Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science [Internet]. 2001 Apr 6;292(5514):110–3.Nielsen SJ, Schneider R, Bauer UM, Bannister AJ, Morrison A, O’Carroll D, et al. Rb targets histone H3 methylation and HP1 to promoters. Nature [Internet]. 2001 Aug 2;412(6846):561–5.Blackburn ML, Chansky HA, Zielinska-Kwiatkowska A, Matsui Y, Yang L. Genomic structure and expression of the mouse ESET gene encoding an ERG-associated histone methyltransferase with a SET domain. Biochim Biophys Acta [Internet]. 2003 Oct 1;1629(1–3):8–14.Du Q, Luu P-L, Stirzaker C, Clark SJ. Methyl-CpG-binding domain proteins: readers of the epigenome. Epigenomics [Internet]. 2015;7(6):1051–73.Lohmann F, Loureiro J, Su H, Fang Q, Lei H, Lewis T, et al. KMT1E mediated H3K9 methylation is required for the maintenance of embryonic stem cells by repressing trophectoderm differentiation. Stem Cells [Internet]. 2010 Feb;28(2):201–12.Yuan P, Han J, Guo G, Orlov YL, Huss M, Loh Y-H, et al. Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells. Genes Dev [Internet]. 2009 Nov 1;23(21):2507–20.An J, Zhang X, Qin J, Wan Y, Hu Y, Liu T, et al. The histone methyltransferase ESET is required for the survival of spermatogonial stem/progenitor cells in mice. Cell Death Dis [Internet]. 2014;5:e1196.Tan S-L, Nishi M, Ohtsuka T, Matsui T, Takemoto K, Kamio-Miura A, et al. Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development. Development [Internet]. 2012 Oct;139(20):3806–16.Matsui T, Leung D, Miyashita H, Maksakova IA, Miyachi H, Kimura H, et al. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature [Internet]. 2010 Apr 8;464(7290):927–31.Kato M, Takemoto K, Shinkai Y. A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing. Nat Commun [Internet]. 2018 Apr 27;9(1):1683.Wu SC, Zhang Y. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol [Internet]. 2010 Sep;11(9):607–20.Ryan RF, Schultz DC, Ayyanathan K, Singh PB, Friedman JR, Fredericks WJ, et al. KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for Krüppel-associated box-zinc finger proteins in heterochromatin-mediated gene silencing. Mol Cell Biol [Internet]. 1999 Jun;19(6):4366–78.Iyengar S, Farnham PJ. KAP1 protein: an enigmatic master regulator of the genome. J Biol Chem [Internet]. 2011 Jul 29;286(30):26267–76.Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev [Internet]. 2002 Apr 15;16(8):919–32.Schultz DC, Friedman JR, Rauscher FJ. Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD. Genes Dev [Internet]. 2001 Feb 15;15(4):428–43.Van Duyne R, Easley R, Wu W, Berro R, Pedati C, Klase Z, et al. Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR. Retrovirology [Internet]. 2008 May 22;5:40.Cho S, Park JS, Kang Y-K. Regulated nuclear entry of over-expressed Setdb1. Genes Cells [Internet]. 2013 Aug;18(8):694–703.Otto A, Schmidt C, Luke G, Allen S, Valasek P, Muntoni F, et al. Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration. J Cell Sci [Internet]. 2008 Sep 1;121(Pt 17):2939–50.Maier VK, Feeney CM, Taylor JE, Creech AL, Qiao JW, Szanto A, et al. Functional Proteomic Analysis of Repressive Histone Methyltransferase Complexes Reveals ZNF518B as a G9A Regulator. Mol Cell Proteomics [Internet]. 2015 Jun;14(6):1435–46.Bian C, Chen Q, Yu X. The zinc finger proteins ZNF644 and WIZ regulate the G9a/GLP complex for gene repression. Elife [Internet]. 2015 Mar 19;4.Frietze S, O’Geen H, Blahnik KR, Jin VX, Farnham PJ. ZNF274 recruits the histone methyltransferase SETDB1 to the 3’ ends of ZNF genes. PLoS One [Internet]. 2010 Dec 8;5(12):e15082.Reed-Inderbitzin E, Moreno-Miralles I, Vanden-Eynden SK, Xie J, Lutterbach B, Durst-Goodwin KL, et al. RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription. Oncogene [Internet]. 2006 Sep 21;25(42):5777–86.Chakraborty S, Sinha KK, Senyuk V, Nucifora G. SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo. Oncogene [Internet]. 2003 Aug 14;22(34):5229–37.Mozzetta C, Pontis J, Fritsch L, Robin P, Portoso M, Proux C, et al. The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing. Mol Cell [Internet]. 2014 Jan 23;53(2):277–89.Fischle W, Franz H, Jacobs SA, Allis CD, Khorasanizadeh S. Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs. J Biol Chem [Internet]. 2008 Jul 11;283(28):19626–35.Mozzetta C, Pontis J, Ait-Si-Ali S. Functional Crosstalk Between Lysine Methyltransferases on Histone Substrates: The Case of G9A/GLP and Polycomb Repressive Complex 2. Antioxid Redox Signal [Internet]. 2015 Jun 1;22(16):1365–81.Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, et al. Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem [Internet]. 2003 Jun 27;278(26):24132–8.Wang H, An W, Cao R, Xia L, Erdjument-Bromage H, Chatton B, et al. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. Mol Cell [Internet]. 2003 Aug;12(2):475–87.Li H, Rauch T, Chen Z-X, Szabó PE, Riggs AD, Pfeifer GP. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem [Internet]. 2006 Jul 14;281(28):19489–500.Murayama A, Ohmori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, et al. Epigenetic control of rDNA loci in response to intracellular energy status. Cell [Internet]. 2008 May 16;133(4):627–39.Ameyar-Zazoua M, Rachez C, Souidi M, Robin P, Fritsch L, Young R, et al. Argonaute proteins couple chromatin silencing to alternative splicing. Nat Struct Mol Biol [Internet]. 2012 Oct;19(10):998–1004.Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, et al. Repression of p53 activity by Smyd2-mediated methylation. Nature [Internet]. 2006 Nov 30;444(7119):629–32.Hamamoto R, Saloura V, Nakamura Y. Critical roles of non-histone protein lysine methylation in human tumorigenesis. Nat Rev Cancer [Internet]. 2015 Feb;15(2):110–24.Zhang X, Tanaka K, Yan J, Li J, Peng D, Jiang Y, et al. Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation. Proc Natl Acad Sci U S A [Internet]. 2013 Oct 22;110(43):17284–9.Saddic LA, West LE, Aslanian A, Yates JR, Rubin SM, Gozani O, et al. Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem [Internet]. 2010 Nov 26;285(48):37733–40.Hamamoto R, Toyokawa G, Nakakido M, Ueda K, Nakamura Y. SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation. Cancer Lett [Internet]. 2014 Aug 28;351(1):126–33.Nishioka K, Chuikov S, Sarma K, Erdjument-Bromage H, Allis CD, Tempst P, et al. Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev [Internet]. 2002 Feb 15;16(4):479–89.Ivanov GS, Ivanova T, Kurash J, Ivanov A, Chuikov S, Gizatullin F, et al. Methylation-acetylation interplay activates p53 in response to DNA damage. Mol Cell Biol [Internet]. 2007 Oct;27(19):6756–69.Kurash JK, Lei H, Shen Q, Marston WL, Granda BW, Fan H, et al. Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo. Mol Cell [Internet]. 2008 Feb 15;29(3):392–400.Yang X-D, Huang B, Li M, Lamb A, Kelleher NL, Chen L-F. Negative regulation of NF-kappaB action by Set9-mediated lysine methylation of the RelA subunit. EMBO J [Internet]. 2009 Apr 22;28(8):1055–66.Ea C-K, Baltimore D. Regulation of NF-kappaB activity through lysine monomethylation of p65. Proc Natl Acad Sci U S A [Internet]. 2009 Nov 10;106(45):18972–7.Munro S, Khaire N, Inche A, Carr S, La Thangue NB. Lysine methylation regulates the pRb tumour suppressor protein. Oncogene [Internet]. 2010 Apr 22;29(16):2357–67.Wang D, Zhou J, Liu X, Lu D, Shen C, Du Y, et al. Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability. Proc Natl Acad Sci U S A [Internet]. 2013 Apr 2;110(14):5516–21.Mulligan P, Westbrook TF, Ottinger M, Pavlova N, Chang B, Macia E, et al. CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation. Mol Cell [Internet]. 2008 Dec 5;32(5):718–26.Huang J, Dorsey J, Chuikov S, Pérez-Burgos L, Zhang X, Jenuwein T, et al. G9a and Glp methylate lysine 373 in the tumor suppressor p53. J Biol Chem [Internet]. 2010 Mar 26;285(13):9636–41.Jacobs SA, Khorasanizadeh S. Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science [Internet]. 2002 Mar 15;295(5562):2080–3.Chin HG, Estève P-O, Pradhan M, Benner J, Patnaik D, Carey MF, et al. Automethylation of G9a and its implication in wider substrate specificity and HP1 binding. Nucleic Acids Res [Internet]. 2007;35(21):7313–23.Rathert P, Dhayalan A, Murakami M, Zhang X, Tamas R, Jurkowska R, et al. Protein lysine methyltransferase G9a acts on non-histone targets. Nat Chem Biol [Internet]. 2008 Jun;4(6):344–6.Ling BMT, Bharathy N, Chung T-K, Kok WK, Li S, Tan YH, et al. Lysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation. Proc Natl Acad Sci U S A [Internet]. 2012 Jan 17;109(3):841–6.Choi J, Jang H, Kim H, Lee J-H, Kim S-T, Cho E-J, et al. Modulation of lysine methylation in myocyte enhancer factor 2 during skeletal muscle cell differentiation. Nucleic Acids Res [Internet]. 2014 Jan;42(1):224–34.Leutz A, Pless O, Lappe M, Dittmar G, Kowenz-Leutz E. Crosstalk between phosphorylation and multi-site arginine/lysine methylation in C/EBPs. Transcription [Internet]. 2(1):3–8.Pless O, Kowenz-Leutz E, Knoblich M, Lausen J, Beyermann M, Walsh MJ, et al. G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta. J Biol Chem [Internet]. 2008 Sep 26;283(39):26357–63.Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, et al. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell [Internet]. 2011 Nov 11;147(4):773–88.Iglesias N, Currie MA, Jih G, Paulo JA, Siuti N, Kalocsay M, et al. Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability. Nature [Internet]. 2018 Jul 23.Piao L, Nakakido M, Suzuki T, Dohmae N, Nakamura Y, Hamamoto R. Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins. Oncotarget [Internet]. 2016 Apr 19;7(16):22846–56.Ryu H, Lee J, Hagerty SW, Soh BY, McAlpin SE, Cormier KA, et al. ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington’s disease. Proc Natl Acad Sci U S A [Internet]. 2006 Dec 12;103(50):19176–81.Lee J, Hwang YJ, Ryu H, Kowall NW, Ryu H. Nucleolar dysfunction in Huntington’s disease. Biochim Biophys Acta [Internet]. 2014 Jun;1842(6):785–90.Chen T, Li E. Structure and function of eukaryotic DNA methyltransferases. Curr Top Dev Biol [Internet]. 2004;60:55–89.Tirado-Magallanes R, Rebbani K, Lim R, Pradhan S, Benoukraf T. Whole genome DNA methylation: beyond genes silencing. Oncotarget [Internet]. 2017 Jan 17;8(3):5629–37.Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E, Jaenisch R, et al. Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development. Genes Dev [Internet]. 2008 Jun 15;22(12):1607–16.Ishida M, Moore GE. The role of imprinted genes in humans. Mol Aspects Med [Internet]. 34(4):826–40.Ito S, D’Alessio AC, Taranova O V, Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature [Internet]. 2010 Aug 26;466(7310):1129–33.Ruzov A, Tsenkina Y, Serio A, Dudnakova T, Fletcher J, Bai Y, et al. Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development. Cell Res [Internet]. 2011 Sep;21(9):1332–42.Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA, et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature [Internet]. 2011 May 19;473(7347):398–402.Leung DC, Dong KB, Maksakova IA, Goyal P, Appanah R, Lee S, et al. Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing. Proc Natl Acad Sci U S A [Internet]. 2011 Apr 5;108(14):5718–23.Dong KB, Maksakova IA, Mohn F, Leung D, Appanah R, Lee S, et al. DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity. EMBO J [Internet]. 2008 Oct 22;27(20):2691–701.Epsztejn-Litman S, Feldman N, Abu-Remaileh M, Shufaro Y, Gerson A, Ueda J, et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat Struct Mol Biol [Internet]. 2008 Nov;15(11):1176–83.Arita K, Isogai S, Oda T, Unoki M, Sugita K, Sekiyama N, et al. Recognition of modification status on a histone H3 tail by linked histone reader modules of the epigenetic regulator UHRF1. Proc Natl Acad Sci U S A [Internet]. 2012 Aug 7;109(32):12950–5.Rothbart SB, Dickson BM, Ong MS, Krajewski K, Houliston S, Kireev DB, et al. Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation. Genes Dev [Internet]. 2013 Jun 1;27(11):1288–98.Girardot M, Cavaillé J, Feil R. Small regulatory RNAs controlled by genomic imprinting and their contribution to human disease. Epigenetics [Internet]. 2012 Dec 1;7(12):1341–8.Barlow DP. Genomic imprinting: a mammalian epigenetic discovery model. Annu Rev Genet [Internet]. 2011;45:379–403.Sanli I, Feil R. Chromatin mechanisms in the developmental control of imprinted gene expression. Int J Biochem Cell Biol [Internet]. 2015 Oct;67:139–47.Barlow DP, Bartolomei MS. Genomic imprinting in mammals. Cold Spring Harb Perspect Biol [Internet]. 2014 Feb 1;6(2).Kota SK, Feil R. Epigenetic transitions in germ cell development and meiosis. Dev Cell [Internet]. 2010 Nov 16;19(5):675–86.Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, et al. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev Cell [Internet]. 2008 Oct;15(4):547–57.Reese KJ, Lin S, Verona RI, Schultz RM, Bartolomei MS. Maintenance of paternal methylation and repression of the imprinted H19 gene requires MBD3. PLoS Genet [Internet]. 2007 Aug;3(8):e137.Ma P, Lin S, Bartolomei MS, Schultz RM. Metastasis tumor antigen 2 (MTA2) is involved in proper imprinted expression of H19 and Peg3 during mouse preimplantation development. Biol Reprod [Internet]. 2010 Dec;83(6):1027–35.Wu M-Y, Tsai T-F, Beaudet AL. Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain. Genes Dev [Internet]. 2006 Oct 15;20(20):2859–70.Pauler FM, Barlow DP, Hudson QJ. Mechanisms of long range silencing by imprinted macro non-coding RNAs. Curr Opin Genet Dev [Internet]. 2012 Jun;22(3):283–9.Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell [Internet]. 2008 Oct 24;32(2):232–46.Li Q, Su Z, Xu X, Liu G, Song X, Wang R, et al. AS1DHRS4, a head-to-head natural antisense transcript, silences the DHRS4 gene cluster in cis and trans. Proc Natl Acad Sci U S A [Internet]. 2012 Aug 28;109(35):14110–5.Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, et al. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science [Internet]. 2008 Dec 12;322(5908):1717–20.Kota SK, Llères D, Bouschet T, Hirasawa R, Marchand A, Begon-Pescia C, et al. ICR noncoding RNA expression controls imprinting and DNA replication at the Dlk1-Dio3 domain. Dev Cell [Internet]. 2014 Oct 13;31(1):19–33.Deininger PL, Batzer MA. Mammalian retroelements. Genome Res [Internet]. 2002 Oct;12(10):1455–65.Faulkner GJ, Carninci P. Altruistic functions for selfish DNA. Cell Cycle [Internet]. 2009 Sep 15;8(18):2895–900.Slotkin RK, Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet [Internet]. 2007 Apr;8(4):272–85.Böhne A, Brunet F, Galiana-Arnoux D, Schultheis C, Volff J-N. Transposable elements as drivers of genomic and biological diversity in vertebrates. Chromosome Res [Internet]. 2008;16(1):203–15.Cordaux R, Batzer MA. The impact of retrotransposons on human genome evolution. Nat Rev Genet [Internet]. 2009 Oct;10(10):691–703.Levin HL, Moran J V. Dynamic interactions between transposable elements and their hosts. Nat Rev Genet [Internet]. 2011 Aug 18;12(9):615–27.Garcia-Perez JL, Widmann TJ, Adams IR. The impact of transposable elements on mammalian development. Development [Internet]. 2016;143(22):4101–14.Mager DL, Stoye JP. Mammalian Endogenous Retroviruses. Microbiol Spectr [Internet]. 2015 Feb;3(1):MDNA3-0009-2014.Boeke J, Stoye J. Retrotransposons, Endogenous Retroviruses, and the Evolution of Retroelements [Internet]. Retroviruses. 1997.Ribet D, Harper F, Dupressoir A, Dewannieux M, Pierron G, Heidmann T. An infectious progenitor for the murine IAP retrotransposon: emergence of an intracellular genetic parasite from an ancient retrovirus. Genome Res [Internet]. 2008 Apr;18(4):597–609.Ribet D, Harper F, Dewannieux M, Pierron G, Heidmann T. Murine MusD retrotransposon: structure and molecular evolution of an “intracellularized” retrovirus. J Virol [Internet]. 2007 Feb;81(4):1888–98.Friedli M, Trono D. The developmental control of transposable elements and the evolution of higher species. Annu Rev Cell Dev Biol [Internet]. 2015;31:429–51.Marchi E, Kanapin A, Magiorkinis G, Belshaw R. Unfixed endogenous retroviral insertions in the human population. J Virol [Internet]. 2014 Sep 1;88(17):9529–37.Kuff EL, Lueders KK. The intracisternal A-particle gene family: structure and functional aspects. Adv Cancer Res [Internet]. 1988;51:183–276.Ribet D, Dewannieux M, Heidmann T. An active murine transposon family pair: retrotransposition of “master” MusD copies and ETn trans-mobilization. Genome Res [Internet]. 2004 Nov;14(11):2261–7.Peaston AE, Evsikov A V, Graber JH, de Vries WN, Holbrook AE, Solter D, et al. Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell [Internet]. 2004 Oct;7(4):597–606.Medstrand P, van de Lagemaat LN, Mager DL. Retroelement distributions in the human genome: variations associated with age and proximity to genes. Genome Res [Internet]. 2002 Oct;12(10):1483–95.Beck CR, Collier P, Macfarlane C, Malig M, Kidd JM, Eichler EE, et al. LINE-1 retrotransposition activity in human genomes. Cell [Internet]. 2010 Jun 25;141(7):1159–70.Elbarbary RA, Lucas BA, Maquat LE. Retrotransposons as regulators of gene expression. Science [Internet]. 2016 Feb 12;351(6274):aac7247.Luan DD, Eickbush TH. RNA template requirements for target DNA-primed reverse transcription by the R2 retrotransposable element. Mol Cell Biol [Internet]. 1995 Jul;15(7):3882–91.Leung DC, Lorincz MC. Silencing of endogenous retroviruses: when and why do histone marks predominate? Trends Biochem Sci [Internet]. 2012 Apr;37(4):127–33.Rowe HM, Trono D. Dynamic control of endogenous retroviruses during development. Virology [Internet]. 2011 Mar 15;411(2):273–87.Collins PL, Kyle KE, Egawa T, Shinkai Y, Oltz EM. The histone methyltransferase SETDB1 represses endogenous and exogenous retroviruses in B lymphocytes. Proc Natl Acad Sci U S A [Internet]. 2015 Jul 7;112(27):8367–72.Liu S, Brind’Amour J, Karimi MM, Shirane K, Bogutz A, Lefebvre L, et al. Setdb1 is required for germline development and silencing of H3K9me3-marked endogenous retroviruses in primordial germ cells. Genes Dev [Internet]. 2014 Sep 15;28(18):2041–55.Rowe HM, Friedli M, Offner S, Verp S, Mesnard D, Marquis J, et al. De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET. Development [Internet]. 2013 Feb 1;140(3):519–29.Leung D, Du T, Wagner U, Xie W, Lee AY, Goyal P, et al. Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1. Proc Natl Acad Sci U S A [Internet]. 2014 May 6;111(18):6690–5.Castro-Diaz N, Ecco G, Coluccio A, Kapopoulou A, Yazdanpanah B, Friedli M, et al. Evolutionally dynamic L1 regulation in embryonic stem cells. Genes Dev [Internet]. 2014 Jul 1;28(13):1397–409.Turelli P, Castro-Diaz N, Marzetta F, Kapopoulou A, Raclot C, Duc J, et al. Interplay of TRIM28 and DNA methylation in controlling human endogenous retroelements. Genome Res [Internet]. 2014 Aug;24(8):1260–70.Maksakova IA, Thompson PJ, Goyal P, Jones SJ, Singh PB, Karimi MM, et al. Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells. Epigenetics Chromatin [Internet]. 2013 Jun 4;6(1):15.Chiba T, Saito T, Yuki K, Zen Y, Koide S, Kanogawa N, et al. Histone lysine methyltransferase SUV39H1 is a potent target for epigenetic therapy of hepatocellular carcinoma. Int J cancer [Internet]. 2015 Jan 15;136(2):289–98.Khanal P, Kim G, Lim S-C, Yun H-J, Lee KY, Choi H-K, et al. Prolyl isomerase Pin1 negatively regulates the stability of SUV39H1 to promote tumorigenesis in breast cancer. FASEB J [Internet]. 2013 Nov;27(11):4606–18.Dworkin AM, Huang TH-M, Toland AE. Epigenetic alterations in the breast: Implications for breast cancer detection, prognosis and treatment. Semin Cancer Biol [Internet]. 2009 Jun;19(3):165–71.Tan J, Yang X, Zhuang L, Jiang X, Chen W, Lee PL, et al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev [Internet]. 2007 May 1;21(9):1050–63.Casciello F, Windloch K, Gannon F, Lee JS. Functional Role of G9a Histone Methyltransferase in Cancer. Front Immunol [Internet]. 2015;6:487.Zhang H, Cai K, Wang J, Wang X, Cheng K, Shi F, et al. MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway. Stem Cells [Internet]. 2014 Nov;32(11):2858–68.Regina C, Compagnone M, Peschiaroli A, Lena A, Annicchiarico-Petruzzelli M, Piro MC, et al. Setdb1, a novel interactor of ΔNp63, is involved in breast tumorigenesis. Oncotarget [Internet].Guo A, Gu H, Zhou J, Mulhern D, Wang Y, Lee KA, et al. Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol Cell Proteomics [Internet]. 2014 Jan;13(1):372–87.Karimi MM, Goyal P, Maksakova IA, Bilenky M, Leung D, Tang JX, et al. DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs. Cell Stem Cell [Internet]. 2011 Jun 3;8(6):676–87.Xu S, Grullon S, Ge K, Peng W. Spatial clustering for identification of ChIP-enriched regions (SICER) to map regions of histone methylation patterns in embryonic stem cells. Methods Mol Biol [Internet]. 2014;1150:97–111.Peters AHFM, Kubicek S, Mechtler K, O’Sullivan RJ, Derijck AAHA, Perez-Burgos L, et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell [Internet]. 2003 Dec;12(6):1577–89.Walter M, Teissandier A, Pérez-Palacios R, Bourc’his D. An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. Elife [Internet]. 2016 Jan 27;5.Kourmouli N, Sun Y, van der Sar S, Singh PB, Brown JP. Epigenetic regulation of mammalian pericentric heterochromatin in vivo by HP1. Biochem Biophys Res Commun [Internet]. 2005 Nov 25;337(3):901–7.Deribe YL, Pawson T, Dikic I. Post-translational modifications in signal integration. Nat Struct Mol Biol [Internet]. 2010 Jun;17(6):666–72.AMBLER RP, REES MW. Epsilon-N-Methyl-lysine in bacterial flagellar protein. Nature [Internet]. 1959 Jul 4;184:56–7.Murn J, Shi Y. The winding path of protein methylation research: milestones and new frontiers. Nat Rev Mol Cell Biol [Internet]. 2017;18(8):517–27.Fischle W, Wang Y, Allis CD. Binary switches and modification cassettes in histone biology and beyond. Nature [Internet]. 2003 Oct 2;425(6957):475–9.Qin R, Cao S, Lyu T, Qi C, Zhang W, Wang Y. CDYL Deficiency Disrupts Neuronal Migration and Increases Susceptibility to Epilepsy. Cell Rep [Internet]. 2017;18(2):380–90.Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev [Internet]. 2003 Aug 1;17(15):1870–81.Thompson PJ, Macfarlan TS, Lorincz MC. Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire. Mol Cell [Internet]. 2016;62(5):766–76.Hutnick LK, Huang X, Loo T-C, Ma Z, Fan G. Repression of retrotransposal elements in mouse embryonic stem cells is primarily mediated by a DNA methylation-independent mechanism. J Biol Chem [Internet]. 2010 Jul 2;285(27):21082–91.Seisenberger S, Peat JR, Reik W. Conceptual links between DNA methylation reprogramming in the early embryo and primordial germ cells. Curr Opin Cell Biol [Internet]. 2013 Jun;25(3):281–8.Leeb M, Pasini D, Novatchkova M, Jaritz M, Helin K, Wutz A. Polycomb complexes act redundantly to repress genomic repeats and genes. Genes Dev [Internet]. 2010 Feb 1;24(3):265–76.Wolf G, Macfarlan TS. Revealing the complexity of retroviral repression. Cell [Internet]. 2015 Sep 24;163(1):30–2.Maksakova IA, Goyal P, Bullwinkel J, Brown JP, Bilenky M, Mager DL, et al. H3K9me3-binding proteins are dispensable for SETDB1/H3K9me3-dependent retroviral silencing. Epigenetics Chromatin [Internet]. 2011 Jul 20;4(1):12.Jamieson K, Wiles ET, McNaught KJ, Sidoli S, Leggett N, Shao Y, et al. Loss of HP1 causes depletion of H3K27me3 from facultative heterochromatin and gain of H3K27me2 at constitutive heterochromatin. Genome Res [Internet]. 2016 Jan;26(1):97–107.Zuo X, Sheng J, Lau H-T, McDonald CM, Andrade M, Cullen DE, et al. Zinc finger protein ZFP57 requires its co-factor to recruit DNA methyltransferases and maintains DNA methylation imprint in embryonic stem cells via its transcriptional repression domain. J Biol Chem [Internet]. 2012 Jan 13;287(3):2107–18.Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, et al. The transcriptional and epigenomic foundations of ground state pluripotency. Cell [Internet]. 2012 Apr 27;149(3):590–604.Pathak R, Feil R. Environmental effects on chromatin repression at imprinted genes and endogenous retroviruses. Curr Opin Chem Biol [Internet]. 2018 May 23;45:139–47.Zhang Y, Yang X, Gui B, Xie G, Zhang D, Shang Y, et al. Corepressor protein CDYL functions as a molecular bridge between polycomb repressor complex 2 and repressive chromatin mark trimethylated histone lysine 27. J Biol Chem [Internet]. 2011 Dec 9;286(49):42414–25.Liu Y, Liu S, Yuan S, Yu H, Zhang Y, Yang X, et al. Chromodomain protein CDYL is required for transmission/restoration of repressive histone marks. J Mol Cell Biol [Internet]. 2017 Jun 1;9(3):178–94.Matouk IJ, Halle D, Gilon M, Hochberg A. The non-coding RNAs of the H19-IGF2 imprinted loci: a focus on biological roles and therapeutic potential in Lung Cancer. J Transl Med [Internet]. 2015 Apr 9;13:113.Beyer S, Pontis J, Schirwis E, Battisti V, Rudolf A, Le Grand F, et al. Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation. Cell Discov [Internet]. 2016;2:16037.Mercatelli N, Beldiman C, Brouard T, Nairismägi M, Kratassiouk G, Largitte L, et al. Mir-205 modulates acinar size and morphology of transformed breast epithelial cells. OncomiRs. 2012;2–9.Jiang Y, Loh Y-HE, Rajarajan P, Hirayama T, Liao W, Kassim BS, et al. The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain. Nat Genet [Internet]. 2017 Aug;49(8):1239–50.Walker CJ, Miranda MA, O’Hern MJ, McElroy JP, Coombes KR, Bundschuh R, et al. Patterns of CTCF and ZFHX3 Mutation and Associated Outcomes in Endometrial Cancer. J Natl Cancer Inst [Internet]. 2015 Nov;107(11).Goke J, Ng HH. CTRL-INSERT: retrotransposons and their contribution to regulation and innovation of the transcriptome. EMBO Rep [Internet]. 2016;17(8):1131–44.instname:Universidad del Rosarioreponame:Repositorio Institucional EdocUREpigénesisGenéticaEvolución & genética575600SETDB1SUV39H1Lysine methylationPost-translational modificationEmbryonic stems cellsSETDB1SUV39H1Metilación de lisinasModificaciones post-traduccionalesCélulas madre embrionariasA trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishmentUn mecanismo de transmetilación entre las dos principales metiltransferasas H3K9 SETDB1 y SUV39H1 regula el establecimiento de heterocromatinaUn mécanisme de trans-méthylation entre les deux principales méthyltransférases de H3K9 SETDB1 et SUV39H1, régule l'établissement de l'hétérochromatinedoctoralThesisTrabajo de gradoTesis de doctoradohttp://purl.org/coar/resource_type/c_db06Escuela de Medicina y Ciencias de la SaludORIGINALCruzTapias-PaolaAndrea-1-2018.pdfCruzTapias-PaolaAndrea-1-2018.pdfapplication/pdf5345327https://repository.urosario.edu.co/bitstreams/ac1f3e8d-beea-4c1a-855a-407962b88251/download97b4923567f4fa36741cfce8c3c808f2MD51CruzTapias-PaolaAndrea-2-2018.pdfCruzTapias-PaolaAndrea-2-2018.pdfapplication/pdf4952886https://repository.urosario.edu.co/bitstreams/c2df54b2-52dd-4a8a-bb7c-7b5d7f30abac/download9e32a0b8bca41d20d5cd480f11fb83b2MD52CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8810https://repository.urosario.edu.co/bitstreams/0804d990-ef8f-4401-959d-d421601bfe47/download9f5eb859bd5c30bc88515135ce7ba417MD54LICENSElicense.txtlicense.txttext/plain1475https://repository.urosario.edu.co/bitstreams/2cf7b16e-416b-4f31-8b7c-b340daf050c4/downloadfab9d9ed61d64f6ac005dee3306ae77eMD53TEXTCruzTapias-PaolaAndrea-1-2018.pdf.txtCruzTapias-PaolaAndrea-1-2018.pdf.txtExtracted texttext/plain119969https://repository.urosario.edu.co/bitstreams/0457879a-1e90-4894-bcf9-2c27c34cbf16/download5a9c175324992f7657dad808f08f76daMD55CruzTapias-PaolaAndrea-2-2018.pdf.txtCruzTapias-PaolaAndrea-2-2018.pdf.txtExtracted texttext/plain150732https://repository.urosario.edu.co/bitstreams/bf18ae70-8b89-4449-a24a-9db1cb01b204/download14c32781c6f946f823ab944eb95bdc94MD57THUMBNAILCruzTapias-PaolaAndrea-1-2018.pdf.jpgCruzTapias-PaolaAndrea-1-2018.pdf.jpgGenerated Thumbnailimage/jpeg4577https://repository.urosario.edu.co/bitstreams/31395790-1ace-4a78-a5d9-61b52b46df4b/download2537fb873b6bdb09b91f39da0580234aMD56CruzTapias-PaolaAndrea-2-2018.pdf.jpgCruzTapias-PaolaAndrea-2-2018.pdf.jpgGenerated Thumbnailimage/jpeg1952https://repository.urosario.edu.co/bitstreams/6865da18-0aff-4254-9cf0-e5d697634451/download42fd8a3d0de1a219dcef00f75e3e68edMD5810336/19828oai:repository.urosario.edu.co:10336/198282021-03-03 19:40:47.827http://creativecommons.org/licenses/by-nc-nd/2.5/co/Atribución-NoComercial-SinDerivadas 2.5 Colombiahttps://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.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

A trans-methylation mechanism between the two major H3K9 methyltransferases SETDB1 and SUV39H1 regulates heterochromatin establishment

Publicaciones similares