H3K9 methyltransferase G9a and the related molecule GLP.

The discovery of Suv39h1, the first SET domain-containing histone lysine methyltransferase (HKMT), was reported in 2000. Since then, research on histone methylation has progressed rapidly. Among the identified HKMTs in mammals, G9a and GLP are the primary enzymes for mono- and dimethylation at Lys 9 of histone H3 (H3K9me1 and H3K9me2), and exist predominantly as a G9a-GLP heteromeric complex that appears to be a functional H3K9 methyltransferase in vivo. Recently, many important studies have reported that G9a and GLP play critical roles in various biological processes. The physiological relevance of G9a/GLP-mediated epigenetic gene regulation is discussed.

[1]  F. Rossi,et al.  Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing , 2011, Proceedings of the National Academy of Sciences.

[2]  Xiaojun Ding,et al.  Histone methyltransferase G9a contributes to H3K27 methylation in vivo , 2011, Cell Research.

[3]  Annette Schenck,et al.  Epigenetic Regulation of Learning and Memory by Drosophila EHMT/G9a , 2011, PLoS biology.

[4]  Ruth I. Tennen,et al.  Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling , 2011, Nature Immunology.

[5]  Xiaojun Ding,et al.  Histone methyltransferase G 9 a contributes to H 3 K 27 methylation in vivo , 2011 .

[6]  Y. Jeng,et al.  H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. , 2012, Cancer research.

[7]  Anton Simeonov,et al.  Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines. , 2010, Journal of medicinal chemistry.

[8]  H. Tamaru.  Confining euchromatin/heterochromatin territory: jumonji crosses the line. , 2010, Genes & development.

[9]  Hee June Choi,et al.  Negative regulation of hypoxic responses via induced Reptin methylation. , 2010, Molecular cell.

[10]  Aiming Sun,et al.  Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases. , 2010, Journal of molecular biology.

[11]  H. Kimura,et al.  Human POGZ modulates dissociation of HP1α from mitotic chromosome arms through Aurora B activation , 2010, Nature Cell Biology.

[12]  Yang Shi,et al.  Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. , 2010, Annual review of biochemistry.

[13]  Anton Simeonov,et al.  A chemiluminescence-based method for identification of histone lysine methyltransferase inhibitors. , 2010, Molecular bioSystems.

[14]  S. Mullaly,et al.  Activating and inhibitory functions for the histone lysine methyltransferase G9a in T helper cell differentiation and function , 2010, The Journal of experimental medicine.

[15]  E. Selker,et al.  DNA methylation and the formation of heterochromatin in Neurospora crassa , 2010, Heredity.

[16]  S. Grewal.  RNAi-dependent formation of heterochromatin and its diverse functions. , 2010, Current opinion in genetics & development.

[17]  B. Garcia,et al.  Histone H1 variant-specific lysine methylation by G9a/KMT1C and Glp1/KMT1D , 2010, Epigenetics & Chromatin.

[18]  Yoichi Shinkai,et al.  Reduced exploration, increased anxiety, and altered social behavior: Autistic-like features of euchromatin histone methyltransferase 1 heterozygous knockout mice , 2010, Behavioural Brain Research.

[19]  H. Kimura,et al.  Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET , 2010, Nature.

[20]  Xiaodong Cheng,et al.  A case study in cross-talk: the histone lysine methyltransferases G9a and GLP , 2010, Nucleic acids research.

[21]  D. Reinberg,et al.  TILRR, a Novel IL-1RI Co-receptor, Potentiates MyD88 Recruitment to Control Ras-dependent Amplification of NF-κB* , 2009, The Journal of Biological Chemistry.

[22]  Annick Harel-Bellan,et al.  A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. , 2010, Molecular cell.

[23]  Paul Greengard,et al.  Essential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity , 2010, Science.

[24]  H. Leonhardt,et al.  The multi-domain protein Np95 connects DNA methylation and histone modification , 2009, Nucleic acids research.

[25]  C. Pikaard,et al.  Arabidopsis Histone Lysine Methyltransferases. , 2010, Advances in botanical research.

[26]  P. Greengard,et al.  Control of Cognition and Adaptive Behavior by the GLP/G9a Epigenetic Suppressor Complex , 2009, Neuron.

[27]  Yoichi Shinkai,et al.  G9a selectively represses a class of late-replicating genes at the nuclear periphery , 2009, Proceedings of the National Academy of Sciences.

[28]  T. Kodama,et al.  Obesity and metabolic syndrome in histone demethylase JHDM2a‐deficient mice , 2009, Genes to cells : devoted to molecular & cellular mechanisms.

[29]  Taiping Chen,et al.  LSD1 demethylates histone and non-histone proteins , 2009, Epigenetics.

[30]  Yi Zhang,et al.  Role of Jhdm2a in regulating metabolic gene expression and obesity resistance , 2009, Nature.

[31]  D. Reinberg,et al.  Dynamic Histone H1 Isotype 4 Methylation and Demethylation by Histone Lysine Methyltransferase G9a/KMT1C and the Jumonji Domain-containing JMJD2/KDM4 Proteins*S⃞ , 2009, Journal of Biological Chemistry.

[32]  M. Walsh,et al.  The ZNF217 oncogene is a candidate organizer of repressive histone modifiers , 2009, Epigenetics.

[33]  J. Snyder,et al.  Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294 , 2009, Nature Structural &Molecular Biology.

[34]  A. Feinberg,et al.  Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells , 2009, Nature Genetics.

[35]  Xiaodong Cheng,et al.  UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications , 2009, Epigenetics.

[36]  S. Jacobsen,et al.  UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells , 2008, Nucleic acids research.

[37]  Jennifer A. Mitchell,et al.  The Air Noncoding RNA Epigenetically Silences Transcription by Targeting G9a to Chromatin , 2008, Science.

[38]  H. Cedar,et al.  De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes , 2008, Nature Structural &Molecular Biology.

[39]  H. Kimura,et al.  G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription , 2008, The EMBO journal.

[40]  D. Schübeler,et al.  DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity , 2008, The EMBO journal.

[41]  M. Reth,et al.  Functional Analysis of Histone Methyltransferase G9a in B and T Lymphocytes1 , 2008, The Journal of Immunology.

[42]  L. Wessels,et al.  Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions , 2008, Nature.

[43]  Xiaodong Cheng,et al.  Protein lysine methyltransferase G9a acts on non-histone targets. , 2008, Nature chemical biology.

[44]  J. Issa,et al.  Downregulation of Histone H3 Lysine 9 Methyltransferase G9a Induces Centrosome Disruption and Chromosome Instability in Cancer Cells , 2008, PloS one.

[45]  S. Berger,et al.  The emerging field of dynamic lysine methylation of non-histone proteins. , 2008, Current opinion in genetics & development.

[46]  Xing Zhang,et al.  The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules , 2008, Nature Structural &Molecular Biology.

[47]  K. Mitsuya,et al.  The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA , 2007, Nature.

[48]  W. Bickmore,et al.  G9a Histone Methyltransferase Contributes to Imprinting in the Mouse Placenta , 2007, Molecular and Cellular Biology.

[49]  J. Qin,et al.  ICBP90, a Novel Methyl K9 H3 Binding Protein Linking Protein Ubiquitination with Heterochromatin Formation , 2007, Molecular and Cellular Biology.

[50]  S. Jacobsen,et al.  UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells , 2007, Science.

[51]  B. Chait,et al.  Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. , 2007, Molecular cell.

[52]  Y. Shinkai,et al.  Functional dynamics of H3K9 methylation during meiotic prophase progression , 2007, The EMBO journal.

[53]  Y. Shinkai,et al.  Identification of ZNF200 as a novel binding partner of histone H3 methyltransferase G9a , 2007, Genes to cells : devoted to molecular & cellular mechanisms.

[54]  Dustin E. Schones,et al.  High-Resolution Profiling of Histone Methylations in the Human Genome , 2007, Cell.

[55]  Yi Zhang,et al.  Regulation of histone methylation by demethylimination and demethylation , 2007, Nature Reviews Molecular Cell Biology.

[56]  I. Henderson,et al.  The SRA Methyl-Cytosine-Binding Domain Links DNA and Histone Methylation , 2007, Current Biology.

[57]  Karl Mechtler,et al.  Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. , 2007, Molecular cell.

[58]  Y. Shinkai.  Regulation and function of H3K9 methylation. , 2007, Sub-cellular biochemistry.

[59]  O. Gangisetty,et al.  Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication. , 2006, Genes & development.

[60]  C. Qian,et al.  SET domain protein lysine methyltransferases: Structure, specificity and catalysis , 2006, Cellular and Molecular Life Sciences CMLS.

[61]  Alex Magee,et al.  Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome. , 2006, American journal of human genetics.

[62]  Y. Shinkai,et al.  Zinc Finger Protein Wiz Links G9a/GLP Histone Methyltransferases to the Co-repressor Molecule CtBP* , 2006, Journal of Biological Chemistry.

[63]  Tomohiro Hayakawa,et al.  Maintenance of self‐renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b , 2006, Genes to cells : devoted to molecular & cellular mechanisms.

[64]  T. Möröy,et al.  Gfi1b alters histone methylation at target gene promoters and sites of γ‐satellite containing heterochromatin , 2006, The EMBO journal.

[65]  O. McDonald,et al.  PRISM/PRDM6, a Transcriptional Repressor That Promotes the Proliferative Gene Program in Smooth Muscle Cells , 2006, Molecular and Cellular Biology.

[66]  H. Erdjument-Bromage,et al.  Histone demethylation by a family of JmjC domain-containing proteins , 2006, Nature.

[67]  Z. Duan,et al.  Gfi1 Coordinates Epigenetic Repression of p21Cip/WAF1 by Recruitment of Histone Lysine Methyltransferase G9a and Histone Deacetylase 1 , 2005, Molecular and Cellular Biology.

[68]  Axel Imhof,et al.  Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9 , 2005, Nature chemical biology.

[69]  Tsutomu Ohta,et al.  Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. , 2005, Genes & development.

[70]  B. D. de Vries,et al.  Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome , 2005, Journal of Medical Genetics.

[71]  E. Selker,et al.  In Vitro and in Vivo Analyses of a Phe/Tyr Switch Controlling Product Specificity of Histone Lysine Methyltransferases* , 2005, Journal of Biological Chemistry.

[72]  Yang Shi,et al.  Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1 , 2004, Cell.

[73]  M. Fraga,et al.  Human DNA Methyltransferase 1 Is Required for Maintenance of the Histone H3 Modification Pattern* , 2004, Journal of Biological Chemistry.

[74]  M. Walsh,et al.  CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[75]  A. Roopra,et al.  Localized domains of G9a-mediated histone methylation are required for silencing of neuronal genes. , 2004, Molecular cell.

[76]  K. Wright,et al.  PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing , 2004, Nature Immunology.

[77]  Beatrix Ueberheide,et al.  Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. , 2003, Molecular cell.

[78]  J. Martens,et al.  Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. , 2003, Molecular cell.

[79]  En Li,et al.  Suv 39 h-Mediated Histone H 3 Lysine 9 Methylation Directs DNA Methylation to Major Satellite Repeats at Pericentric Heterochromatin , 2003 .

[80]  J. Bender,et al.  An Arabidopsis SET domain protein required for maintenance but not establishment of DNA methylation , 2002, The EMBO journal.

[81]  H. Kato,et al.  G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. , 2002, Genes & development.

[82]  David M. Livingston,et al.  A Complex with Chromatin Modifiers That Occupies E2F- and Myc-Responsive Genes in G0 Cells , 2002, Science.

[83]  J. P. Jackson,et al.  Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase , 2002, Nature.

[84]  Kenneth Y. Tsai,et al.  Control of CpNpG DNA methylation by the KRYPTONITE histone H 3 methyltransferase , 2002 .

[85]  E. Selker,et al.  A histone H3 methyltransferase controls DNA methylation in Neurospora crassa , 2001, Nature.

[86]  Yoichi Shinkai,et al.  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* , 2001, The Journal of Biological Chemistry.

[87]  Karl Mechtler,et al.  Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins , 2001, Nature.

[88]  Andrew J. Bannister,et al.  Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain , 2001, Nature.

[89]  C. Ponting,et al.  Regulation of chromatin structure by site-specific histone H3 methyltransferases , 2000, Nature.

[90]  T. Jenuwein,et al.  SET domain proteins modulate chromatin domains in eu- and heterochromatin , 1998, Cellular and Molecular Life Sciences CMLS.

[91]  N. Sonenberg,et al.  UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells , 2007, Science.