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Commentary

The expanding role of the Ehmt2/G9a complex in neurodevelopment

, &
Article: e1316888 | Received 10 Jan 2017, Accepted 30 Mar 2017, Published online: 19 May 2017

References

  • Tachibana M, Sugimoto K, Fukushima T, Shinkai Y. Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem 2001; 276:25309-17; PMID:11316813; https://doi.org/10.1074/jbc.M101914200
  • Rice JC, Briggs SD, Ueberheide B, Barber CM, Shabanowitz J, Hunt DF, Shinkai Y, Allis CD. Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. Mol Cell 2003; 12:1591-8; PMID:14690610; https://doi.org/10.1016/S1097-2765(03)00479-9
  • Yu Y, Song C, Zhang Q, DiMaggio PA, Garcia BA, York A, Carey MF, Grunstein M. Histone H3 lysine 56 methylation regulates DNA replication through its interaction with PCNA. Mol Cell 2012; 46:7-17; PMID:22387026; https://doi.org/10.1016/j.molcel.2012.01.019
  • Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA, Perez-Burgos L, Kohlmaier A, Opravil S, Tachibana M, Shinkai Y, et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell 2003; 12:1577-89; PMID:14690609; https://doi.org/10.1016/S1097-2765(03)00477-5
  • Herz HM, Garruss A, Shilatifard A. SET for life: biochemical activities and biological functions of SET domain-containing proteins. Trends Biochem Sci 2013; 38:621-39; PMID:24148750; https://doi.org/10.1016/j.tibs.2013.09.004
  • Purcell DJ, Jeong KW, Bittencourt D, Gerke DS, Stallcup MR. A distinct mechanism for coactivator versus corepressor function by histone methyltransferase G9a in transcriptional regulation. J Biol Chem 2011; 286:41963-71; PMID:21984853; https://doi.org/10.1074/jbc.M111.298463
  • Collins RE, Northrop JP, Horton JR, Lee DY, Zhang X, Stallcup MR, Cheng X. The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules. Nat Struct Mol Biol 2008; 15:245-50; PMID:18264113; https://doi.org/10.1038/nsmb.1384
  • Milner CM, Campbell RD. The G9a gene in the human major histocompatibility complex encodes a novel protein containing ankyrin-like repeats. Biochem J 1993; 290(Pt 3):811-8; PMID:8457211; https://doi.org/10.1042/bj2900811
  • Tachibana M, Ueda J, Fukuda M, Takeda N, Ohta T, Iwanari H, Sakihama T, Kodama T, Hamakubo T, Shinkai Y. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev 2005; 19:815-26; PMID:15774718; https://doi.org/10.1101/gad.1284005
  • Simon JM, Parker JS, Liu F, Rothbart SB, Ait-Si-Ali S, Strahl BD, Jin J, Davis IJ, Mosley AL, Pattenden SG. A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin. J Biol Chem 2015; 290:26088-102; PMID:26338712; https://doi.org/10.1074/jbc.M115.654459
  • Bian C, Chen Q, Yu X. The zinc finger proteins ZNF644 and WIZ regulate the G9a/GLP complex for gene repression. Elife 2015; 4:e05606.
  • Maier VK, Feeney CM, Taylor JE, Creech AL, Qiao JW, Szanto A, Das PP, Chevrier N, Cifuentes-Rojas C, Orkin SH, et al. Functional Proteomic Analysis of Repressive Histone Methyltransferase Complexes Reveals ZNF518B as a G9A Regulator. Mol Cell Proteomics 2015; 14:1435-46; PMID:25680957; https://doi.org/10.1074/mcp.M114.044586
  • Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, Fraser P. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 2008; 322:1717-20; PMID:18988810; https://doi.org/10.1126/science.1163802
  • Chaturvedi CP, Somasundaram B, Singh K, Carpenedo RL, Stanford WL, Dilworth FJ, Brand M. Maintenance of gene silencing by the coordinate action of the H3K9 methyltransferase G9a/KMT1C and the H3K4 demethylase Jarid1a/KDM5A. Proc Natl Acad Sci U S A 2012; 109:18845-50; PMID:23112189; https://doi.org/10.1073/pnas.1213951109
  • Shi Y, Sawada J, Sui G, Affar el B, Whetstine JR, Lan F, Ogawa H, Luke MP, Nakatani Y, Shi Y. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature 2003; 422:735-8; PMID:12700765; https://doi.org/10.1038/nature01550
  • Duan Z, Zarebski A, Montoya-Durango D, Grimes HL, Horwitz M. Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Mol Cell Biol 2005; 25:10338-51; PMID:16287849; https://doi.org/10.1128/MCB.25.23.10338-10351.2005
  • Wang L, Charroux B, Kerridge S, Tsai CC. Atrophin recruits HDAC1/2 and G9a to modify histone H3K9 and to determine cell fates. EMBO Rep 2008; 9:555-62; PMID:18451879; https://doi.org/10.1038/embor.2008.67
  • El Gazzar M, Yoza BK, Chen X, Hu J, Hawkins GA, McCall CE. G9a and HP1 couple histone and DNA methylation to TNFalpha transcription silencing during endotoxin tolerance. J Biol Chem 2008; 283:32198-208; PMID:18809684; https://doi.org/10.1074/jbc.M803446200
  • Chin HG, Esteve PO, Pradhan M, Benner J, Patnaik D, Carey MF, Pradhan S. Automethylation of G9a and its implication in wider substrate specificity and HP1 binding. Nucleic Acids Res 2007; 35:7313-23; PMID:17962312; https://doi.org/10.1093/nar/gkm726
  • Kim JK, Esteve PO, Jacobsen SE, Pradhan S. UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells. Nucleic Acids Res 2009; 37:493-505; PMID:19056828; https://doi.org/10.1093/nar/gkn961
  • Rai K, Jafri IF, Chidester S, James SR, Karpf AR, Cairns BR, Jones DA. Dnmt3 and G9a cooperate for tissue-specific development in zebrafish. J Biol Chem 2010; 285:4110-21; PMID:19946145; https://doi.org/10.1074/jbc.M109.073676
  • Han P, Li W, Yang J, Shang C, Lin CH, Cheng W, Hang CT, Cheng HL, Chen CH, Wong J, et al. Epigenetic response to environmental stress: Assembly of BRG1-G9a/GLP-DNMT3 repressive chromatin complex on Myh6 promoter in pathologically stressed hearts. Biochim Biophys Acta 2016; 1863:1772-81; PMID:26952936; https://doi.org/10.1016/j.bbamcr.2016.03.002
  • Olsen JB, Wong L, Deimling S, Miles A, Guo H, Li Y, Zhang Z, Greenblatt JF, Emili A, Tropepe V. G9a and ZNF644 physically associate to suppress progenitor gene expression during neurogenesis. Stem Cell Rep 2016; 7:454-70; PMID:27546533; https://doi.org/10.1016/j.stemcr.2016.06.012
  • Liu N, Zhang Z, Wu H, Jiang Y, Meng L, Xiong J, Zhao Z, Zhou X, Li J, Li H, et al. Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability. Genes Dev 2015; 29:379-93; PMID:25637356; https://doi.org/10.1101/gad.254425.114
  • Inagawa M, Nakajima K, Makino T, Ogawa S, Kojima M, Ito S, Ikenishi A, Hayashi T, Schwartz RJ, Nakamura K, et al. Histone H3 lysine 9 methyltransferases, G9a and GLP are essential for cardiac morphogenesis. Mech Dev 2013; 130:519-31; PMID:23892084; https://doi.org/10.1016/j.mod.2013.07.002
  • Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H, et al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev 2002; 16:1779-91; PMID:12130538; https://doi.org/10.1101/gad.989402
  • Cunliffe VT. Histone modifications in zebrafish development. Methods Cell Biol 2016; 135:361-85; PMID:27443936
  • Lawrence M, Daujat S, Schneider R. Lateral thinking: how histone modifications regulate gene expression. Trends Genet 2016; 32:42-56; PMID:26704082; https://doi.org/10.1016/j.tig.2015.10.007
  • Zylicz JJ, Dietmann S, Gunesdogan U, Hackett JA, Cougot D, Lee C, Surani MA. Chromatin dynamics and the role of G9a in gene regulation and enhancer silencing during early mouse development. Elife 2015; 4:pii: e09571; PMID:26551560; https://doi.org/10.7554/eLife.09571
  • Mozzetta C, Pontis J, Fritsch L, Robin P, Portoso M, Proux C, Margueron R, Ait-Si-Ali S. The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing. Mol Cell 2014; 53:277-89; PMID:24389103; https://doi.org/10.1016/j.molcel.2013.12.005
  • Pan MR, Hsu MC, Chen LT, Hung WC. G9a orchestrates PCL3 and KDM7A to promote histone H3K27 methylation. Sci Rep 2015; 5:18709; PMID:26688070; https://doi.org/10.1038/srep18709
  • Epsztejn-Litman S, Feldman N, Abu-Remaileh M, Gerson A, Ueda J, Deplus R, Fuks F, Shinkai Y, Cedar H, Bergman Y. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat Struct Mol Biol 2008; 15:1176-83; PMID:18953337; https://doi.org/10.1038/nsmb.1476
  • Xin Z, Tachibana M, Guggiari M, Heard E, Shinkai Y, Wagstaff J. Role of histone methyltransferase G9a in CpG methylation of the Prader-Willi syndrome imprinting center. J Biol Chem 2003; 278:14996-5000; PMID:12586828; https://doi.org/10.1074/jbc.M211753200
  • Wen B, Wu H, Shinkai Y, Irizarry RA, Feinberg AP. Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat Genet 2009; 41:246-50; PMID:19151716; https://doi.org/10.1038/ng.297
  • Filion GJ, van Steensel B. Reassessing the abundance of H3K9me2 chromatin domains in embryonic stem cells. Nat Genet 2010; 42:4; author reply 5-6; https://doi.org/10.1038/ng0110-4
  • Lienert F, Mohn F, Tiwari VK, Baubec T, Roloff TC, Gaidatzis D, Stadler MB, Schübeler D. Genomic prevalence of heterochromatic H3K9me2 and transcription do not discriminate pluripotent from terminally differentiated cells. PLoS Genet 2011; 7:e1002090; PMID:21655081; https://doi.org/10.1371/journal.pgen.1002090
  • Zhang T, Termanis A, Ozkan B, Bao XX, Culley J, de Lima Alves F, Rappsilber J, Ramsahoye B, Stancheva I. G9a/GLP complex maintains imprinted DNA methylation in embryonic stem cells. Cell Rep 2016; 15:77-85; PMID:27052169; https://doi.org/10.1016/j.celrep.2016.03.007
  • Chen P, Yao JF, Huang RF, Zheng FF, Jiang XH, Chen X, Chen J, Li M, Huang HF, Jiang YP, et al. Effect of BIX-01294 on H3K9me2 levels and the imprinted gene Snrpn in mouse embryonic fibroblast cells. Biosci Rep 2015; 35:pii:e00257; https://doi.org/10.1042/BSR20150064
  • Wagschal A, Sutherland HG, Woodfine K, Henckel A, Chebli K, Schulz R, Oakey RJ, Bickmore WA, Feil R. G9a histone methyltransferase contributes to imprinting in the mouse placenta. Mol Cell Biol 2008; 28:1104-13; PMID:18039842; https://doi.org/10.1128/MCB.01111-07
  • Chen X, Skutt-Kakaria K, Davison J, Ou YL, Choi E, Malik P, Loeb K, Wood B, Georges G, Torok-Storb B, et al. G9a/GLP-dependent histone H3K9me2 patterning during human hematopoietic stem cell lineage commitment. Genes Dev 2012; 26:2499-511; PMID:23105005; https://doi.org/10.1101/gad.200329.112
  • Ugarte F, Sousae R, Cinquin B, Martin EW, Krietsch J, Sanchez G, Inman M, Tsang H, Warr M, Passegué E, et al. Progressive chromatin condensation and H3K9 methylation regulate the differentiation of embryonic and hematopoietic stem cells. Stem Cell Reports 2015; 5:728-40; PMID:26489895; https://doi.org/10.1016/j.stemcr.2015.09.009
  • Katoh K, Yamazaki R, Onishi A, Sanuki R, Furukawa T. G9a histone methyltransferase activity in retinal progenitors is essential for proper differentiation and survival of mouse retinal cells. J Neurosci 2012; 32:17658-70; PMID:23223288; https://doi.org/10.1523/JNEUROSCI.1869-12.2012
  • Rao VK, Ow JR, Shankar SR, Bharathy N, Manikandan J, Wang Y, Taneja R. G9a promotes proliferation and inhibits cell cycle exit during myogenic differentiation. Nucleic Acids Res 2016; 44:8129-43; PMID:27229136; https://doi.org/10.1093/nar/gkw483
  • Rao RC, Tchedre KT, Malik MT, Coleman N, Fang Y, Marquez VE, Chen DF. Dynamic patterns of histone lysine methylation in the developing retina. Invest Ophthalmol Vis Sci 2010; 51:6784-92; PMID:20671280; https://doi.org/10.1167/iovs.09-4730
  • Lee DY, Northrop JP, Kuo MH, Stallcup MR. Histone H3 lysine 9 methyltransferase G9a is a transcriptional coactivator for nuclear receptors. J Biol Chem 2006; 281:8476-85; PMID:16461774; https://doi.org/10.1074/jbc.M511093200
  • Oh ST, Kim KB, Chae YC, Kang JY, Hahn Y, Seo SB. H3K9 histone methyltransferase G9a-mediated transcriptional activation of p21. FEBS Lett 2014; 588:685-91; PMID:24492005; https://doi.org/10.1016/j.febslet.2014.01.039
  • Chaturvedi CP, Hosey AM, Palii C, Perez-Iratxeta C, Nakatani Y, Ranish JA, Dilworth FJ, Brand M. Dual role for the methyltransferase G9a in the maintenance of beta-globin gene transcription in adult erythroid cells. Proc Natl Acad Sci U S A 2009; 106:18303-8; PMID:19822740; https://doi.org/10.1073/pnas.0906769106
  • Bittencourt D, Wu DY, Jeong KW, Gerke DS, Herviou L, Ianculescu I, Chodankar R, Siegmund KD, Stallcup MR. G9a functions as a molecular scaffold for assembly of transcriptional coactivators on a subset of glucocorticoid receptor target genes. Proc Natl Acad Sci U S A 2012; 109:19673-8; PMID:23151507; https://doi.org/10.1073/pnas.1211803109
  • Purcell DJ, Khalid O, Ou CY, Little GH, Frenkel B, Baniwal SK, Stallcup MR. Recruitment of coregulator G9a by Runx2 for selective enhancement or suppression of transcription. J Cell Biochem 2012; 113:2406-14; PMID:22389001; https://doi.org/10.1002/jcb.24114
  • Ohno H, Shinoda K, Ohyama K, Sharp LZ, Kajimura S. EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature 2013; 504:163-7; PMID:24196706; https://doi.org/10.1038/nature12652
  • Wang L, Xu S, Lee JE, Baldridge A, Grullon S, Peng W, Ge K. Histone H3K9 methyltransferase G9a represses PPARgamma expression and adipogenesis. EMBO J 2013; 32:45-59; PMID:23178591; https://doi.org/10.1038/emboj.2012.306
  • Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med 2013; 3:a011643; PMID:23209159; https://doi.org/10.1101/cshperspect.a011643
  • Rada M, Vasileva E, Lezina L, Marouco D, Antonov AV, Macip S, Melino G, Barlev NA. Human EHMT2/G9a activates p53 through methylation-independent mechanism. Oncogene 2017; 36:922-32; PMID:27452519; https://doi.org/10.1038/onc.2016.258
  • Brown SE, Campbell RD, Sanderson CM. Novel NG36/G9a gene products encoded within the human and mouse MHC class III regions. Mamm Genome 2001; 12:916-24; PMID:11707778; https://doi.org/10.1007/s00335-001-3029-3
  • Mauger O, Klinck R, Chabot B, Muchardt C, Allemand E, Batsche E. Alternative splicing regulates the expression of G9A and SUV39H2 methyltransferases, and dramatically changes SUV39H2 functions. Nucleic Acids Res 2015; 43:1869-82; PMID:25605796; https://doi.org/10.1093/nar/gkv013
  • Fiszbein A, Giono LE, Quaglino A, Berardino BG, Sigaut L, von Bilderling C, Schor IE, Steinberg JH, Rossi M, Pietrasanta LI, et al. Alternative Splicing of G9a Regulates Neuronal Differentiation. Cell Rep 2016; 14:2797-808; PMID:26997278; https://doi.org/10.1016/j.celrep.2016.02.063
  • Lim S, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development 2013; 140:3079-93; PMID:23861057; https://doi.org/10.1242/dev.091744
  • Fisher RP. Getting to S: CDK functions and targets on the path to cell-cycle commitment. F1000Res 2016; 5:2374; PMID:27746911; https://doi.org/10.12688/f1000research.9463.1
  • Shaltiel IA, Krenning L, Bruinsma W, Medema RH. The same, only different - DNA damage checkpoints and their reversal throughout the cell cycle. J Cell Sci 2015; 128:607-20; PMID:25609713; https://doi.org/10.1242/jcs.163766
  • Giono LE, Manfredi JJ. The p53 tumor suppressor participates in multiple cell cycle checkpoints. J Cell Physiol 2006; 209:13-20; PMID:16741928; https://doi.org/10.1002/jcp.20689
  • Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991; 51:6304-11; PMID:1933891
  • Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A 1992; 89:7491-95; PMID:1323840; https://doi.org/10.1073/pnas.89.16.7491
  • Fischer NW, Prodeus A, Malkin D, Gariepy J. p53 oligomerization status modulates cell fate decisions between growth, arrest and apoptosis. Cell Cycle 2016; 15(23):3210-9
  • Hupp TR, Meek DW, Midgley CA, Lane DP. Regulation of the specific DNA binding function of p53. Cell 1992; 71:875-86; PMID:1423635; https://doi.org/10.1016/0092-8674(92)90562-Q
  • Zhang W, McClain C, Gau JP, Guo XY, Deisseroth AB. Hyperphosphorylation of p53 induced by okadaic acid attenuates its transcriptional activation function. Cancer Res 1994; 54:4448-53; PMID:8044794
  • Mayr GA, Reed M, Wang P, Wang Y, Schweds JF, Tegtmeyer P. Serine phosphorylation in the NH2 terminus of p53 facilitates transactivation. Cancer Res 1995; 55:2410-7; PMID:7757994
  • Takenaka I, Morin F, Seizinger BR, Kley N. Regulation of the sequence-specific DNA binding function of p53 by protein kinase C and protein phosphatases. J Biol Chem 1995; 270:5405-11; PMID:7534296; https://doi.org/10.1074/jbc.270.10.5405
  • Dulic V, Kaufmann WK, Wilson SJ, Tlsty TD, Lees E, Harper JW, Elledge SJ, Reed SI. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 1994; 76:1013-23; PMID:8137420; https://doi.org/10.1016/0092-8674(94)90379-4
  • el-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 1994; 54:1169-74; PMID:8118801
  • Fischer M, Quaas M, Steiner L, Engeland K. The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes. Nucleic Acids Res 2016; 44:164-74; PMID:26384566; https://doi.org/10.1093/nar/gkv927
  • Lo PK, Lee JS, Sukumar S. The p53-p21WAF1 checkpoint pathway plays a protective role in preventing DNA rereplication induced by abrogation of FOXF1 function. Cell Signal 2012; 24:316-24; PMID:21964066; https://doi.org/10.1016/j.cellsig.2011.09.017
  • He G, Siddik ZH, Huang Z, Wang R, Koomen J, Kobayashi R, Khokhar AR, Kuang J. Induction of p21 by p53 following DNA damage inhibits both Cdk4 and Cdk2 activities. Oncogene 2005; 24:2929-43; PMID:15735718; https://doi.org/10.1038/sj.onc.1208474
  • Brugarolas J, Moberg K, Boyd SD, Taya Y, Jacks T, Lees JA. Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after gamma-irradiation. Proc Natl Acad Sci U S A 1999; 96:1002-7; PMID:9927683; https://doi.org/10.1073/pnas.96.3.1002
  • Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 1994; 9:1799-805; PMID:8183579
  • Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 1995; 80:293-9; PMID:7834749; https://doi.org/10.1016/0092-8674(95)90513-8
  • Selvakumaran M, Lin HK, Miyashita T, Wang HG, Krajewski S, Reed JC, Hoffman B, Liebermann D. Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways. Oncogene 1994; 9:1791-8; PMID:8183578
  • Zhan Q, Fan S, Bae I, Guillouf C, Liebermann DA, O'Connor PM, Fornace AJ Jr. Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene 1994; 9:3743-51; PMID:7970735
  • Huang J, Dorsey J, Chuikov S, Pérez-Burgos L, Zhang X, Jenuwein T, Reinberg D, Berger SL. G9a and Glp methylate lysine 373 in the tumor suppressor p53. J Biol Chem 2010; 285:9636-41; PMID:20118233; https://doi.org/10.1074/jbc.M109.062588
  • Chen L, Li Z, Zwolinska AK, Smith MA, Cross B, Koomen J, Yuan ZM, Jenuwein T, Marine JC, Wright KL, et al. MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output. EMBO J 2010; 29:2538-52; PMID:20588255; https://doi.org/10.1038/emboj.2010.140
  • Wu R, Terry AV, Singh PB, Gilbert DM. Differential subnuclear localization and replication timing of histone H3 lysine 9 methylation states. Mol Biol Cell 2005; 16:2872-81; PMID:15788566; https://doi.org/10.1091/mbc.E04-11-0997
  • Yokochi T, Poduch K, Ryba T, Lu J, Hiratani I, Tachibana M, Shinkai Y, Gilbert DM. G9a selectively represses a class of late-replicating genes at the nuclear periphery. Proc Natl Acad Sci U S A 2009; 106:19363-8; PMID:19889976; https://doi.org/10.1073/pnas.0906142106
  • Jorgensen HF, Azuara V, Amoils S, Spivakov M, Terry A, Nesterova T, Cobb BS, Ramsahoye B, Merkenschlager M, Fisher AG. The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells. Genome Biol 2007; 8:R169; PMID:17705870; https://doi.org/10.1186/gb-2007-8-8-r169
  • Dungrawala H, Rose KL, Bhat KP, Mohni KN, Glick GG, Couch FB, Cortez D. The replication checkpoint prevents two types of fork collapse without regulating replisome stability. Mol Cell 2015; 59:998-1010; PMID:26365379; https://doi.org/10.1016/j.molcel.2015.07.030
  • Zhang X, Wen H, Shi X. Lysine methylation: beyond histones. Acta Biochim Biophys Sin (Shanghai) 2012; 44:14-27; PMID:22194010; https://doi.org/10.1093/abbs/gmr100
  • Lee JY, Lee SH, Heo SH, Kim KS, Kim C, Kim DK, Ko JJ, Park KS. Novel Function of Lysine Methyltransferase G9a in the Regulation of Sox2 Protein Stability. PLoS One 2015; 10:e0141118; PMID:26492085; https://doi.org/10.1371/journal.pone.0141118
  • Oh SY, Seok JY, Choi YS, Lee SH, Bae JS, Lee YM. The Histone Methyltransferase Inhibitor BIX01294 Inhibits HIF-1alpha Stability and Angiogenesis. Mol Cells 2015; 38:528-34; PMID:26013382; https://doi.org/10.14348/molcells.2015.0026
  • Kontaki H, Talianidis I. Lysine methylation regulates E2F1-induced cell death. Mol Cell 2010; 39:152-60; PMID:20603083; https://doi.org/10.1016/j.molcel.2010.06.006
  • Jung ES, Sim YJ, Jeong HS, Kim SJ, Yun YJ, Song JH, Jeon SH, Choe C, Park KT, Kim CH, et al. Jmjd2C increases MyoD transcriptional activity through inhibiting G9a-dependent MyoD degradation. Biochim Biophys Acta 2015; 1849:1081-94; PMID:26149774; https://doi.org/10.1016/j.bbagrm.2015.07.001
  • Kondo Y, Shen L, Ahmed S, Boumber Y, Sekido Y, Haddad BR, Issa JP. Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. PLoS One 2008; 3:e2037; PMID:18446223; https://doi.org/10.1371/journal.pone.0002037
  • Fritsch L, Robin P, Mathieu JR, Souidi M, Hinaux H, Rougeulle C, Harel-Bellan A, Ameyar-Zazoua M, Ait-Si-Ali S. A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Mol Cell 2010; 37:46-56; PMID:20129054; https://doi.org/10.1016/j.molcel.2009.12.017
  • Giri S, Aggarwal V, Pontis J, Shen Z, Chakraborty A, Khan A, Mizzen C, Prasanth KV, Ait-Si-Ali S, Ha T, et al. The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin. Elife 2015; 4:e06496; PMID:25922909; https://doi.org/10.7554/eLife.06496
  • Giri S, Prasanth SG. Association of ORCA/LRWD1 with repressive histone methyl transferases mediates heterochromatin organization. Nucleus 2015; 6:435-41; PMID:26765314; https://doi.org/10.1080/19491034.2015.1102814
  • Verdaasdonk JS, Bloom K. Centromeres: unique chromatin structures that drive chromosome segregation. Nat Rev Mol Cell Biol 2011; 12:320-32; PMID:21508988; https://doi.org/10.1038/nrm3107
  • Garcez PP, Diaz-Alonso J, Crespo-Enriquez I, Castro D, Bell D, Guillemot F. Cenpj/CPAP regulates progenitor divisions and neuronal migration in the cerebral cortex downstream of Ascl1. Nat Commun 2015; 6:6474; PMID:25753651; https://doi.org/10.1038/ncomms7474
  • Bazzi H, Anderson KV. Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo. Proc Natl Acad Sci U S A 2014; 111:E1491-500; PMID:24706806; https://doi.org/10.1073/pnas.1400568111

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