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PMID: 15774718 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9.

Genes & development ·Vol. 19 ·No. 7 ·2005-04-01 ·Pages 815-26

Tachibana M, Ueda J, Fukuda M, Takeda N, Ohta T, Iwanari H, Sakihama T, Kodama T, Hamakubo T, Shinkai Y

Abstract

Histone H3 Lys 9 (H3-K9) methylation is a crucial epigenetic mark for transcriptional silencing. G9a is the major mammalian H3-K9 methyltransferase that targets euchromatic regions and is essential for murine embryogenesis. There is a single G9a-related methyltransferase in mammals, called GLP/Eu-HMTase1. Here we show that GLP is also important for H3-K9 methylation of mouse euchromatin. GLP-deficiency led to embryonic lethality, a severe reduction of H3-K9 mono- and dimethylation, the induction of Mage-a gene expression, and HP1 relocalization in embryonic stem cells, all of which were phenotypes of G9a-deficiency. Furthermore, we show that G9a and GLP formed a stoichiometric heteromeric complex in a wide variety of cell types. Biochemical analyses revealed that formation of the G9a/GLP complex was dependent on their enzymatic SET domains. Taken together, our new findings revealed that G9a and GLP cooperatively exert H3-K9 methyltransferase function in vivo, likely through the formation of higher-order heteromeric complexes.

MeSH Terms
Animals Euchromatin/enzymology Histone Methyltransferases Histone-Lysine N-Methyltransferase/chemistry,metabolism Histones/metabolism Lysine/metabolism Methylation Mice Protein Methyltransferases Protein Structure, Quaternary Stem Cells/enzymology
Chemicals
Euchromatin Histones Histone Methyltransferases Protein Methyltransferases GLP protein, mouse Histone-Lysine N-Methyltransferase Lysine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Tachibana Makoto
Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Ueda Jun
Fukuda Mikiko
Takeda Naoki
Ohta Tsutomu
Iwanari Hiroko
Sakihama Toshiko
Kodama Tatsuhiko
Hamakubo Takao
Shinkai Yoichi
References (40)
40 references, click to expand
  1. Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase.
    Curr Biol. 2002 Jul 9;12(13):1086-99 PMID: 12121615
  2. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.
    Cell. 2001 Nov 2;107(3):323-37 PMID: 11701123
  3. The generation of monoclonal antibodies against human peroxisome proliferator-activated receptors (PPARs).
    J Atheroscler Thromb. 2002;9(5):233-42 PMID: 12409633
  4. Modulation of heterochromatin protein 1 dynamics in primary Mammalian cells.
    Science. 2003 Jan 31;299(5607):719-21 PMID: 12560554
  5. Maintenance of stable heterochromatin domains by dynamic HP1 binding.
    Science. 2003 Jan 31;299(5607):721-5 PMID: 12560555
  6. A dimeric viral SET domain methyltransferase specific to Lys27 of histone H3.
    Nat Struct Biol. 2003 Mar;10(3):187-96 PMID: 12567185
  7. Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor.
    Oncogene. 2002 Jan 3;21(1):148-52 PMID: 11791185
  8. 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. 2002 Apr 15;16(8):919-32 PMID: 11959841
  9. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells.
    Science. 2002 May 10;296(5570):1132-6 PMID: 12004135
  10. The many faces of histone lysine methylation.
    Curr Opin Cell Biol. 2002 Jun;14(3):286-98 PMID: 12067650
  11. PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin.
    Mol Cell. 2002 Jun;9(6):1201-13 PMID: 12086618
  12. Coordinated histone modifications mediated by a CtBP co-repressor complex.
    Nature. 2003 Apr 17;422(6933):735-8 PMID: 12700765
  13. An epigenetic road map for histone lysine methylation.
    J Cell Sci. 2003 Jun 1;116(Pt 11):2117-24 PMID: 12730288
  14. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains.
    Genes Dev. 2003 Aug 1;17(15):1870-81 PMID: 12897054
  15. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression.
    Mol Cell. 2003 Aug;12(2):475-87 PMID: 14536086
  16. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin.
    Mol Cell. 2003 Dec;12(6):1577-89 PMID: 14690609
  17. Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains.
    Mol Cell. 2003 Dec;12(6):1591-8 PMID: 14690610
  18. PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing.
    Nat Immunol. 2004 Mar;5(3):299-308 PMID: 14985713
  19. Targeted inhibition of V(D)J recombination by a histone methyltransferase.
    Nat Immunol. 2004 Mar;5(3):309-16 PMID: 14985714
  20. Histone H3-K9 methyltransferase ESET is essential for early development.
    Mol Cell Biol. 2004 Mar;24(6):2478-86 PMID: 14993285
  21. The N-terminus of Drosophila SU(VAR)3-9 mediates dimerization and regulates its methyltransferase activity.
    Biochemistry. 2004 Mar 30;43(12):3740-9 PMID: 15035645
  22. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin.
    Genes Dev. 2004 Jun 1;18(11):1251-62 PMID: 15145825
  23. The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3.
    Curr Opin Genet Dev. 2004 Apr;14(2):155-64 PMID: 15196462
  24. Localized domains of G9a-mediated histone methylation are required for silencing of neuronal genes.
    Mol Cell. 2004 Jun 18;14(6):727-38 PMID: 15200951
  25. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex.
    Mol Cell. 2004 Jul 2;15(1):57-67 PMID: 15225548
  26. CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription.
    Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11257-62 PMID: 15269344
  27. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly.
    Mol Cell. 2004 Aug 27;15(4):595-605 PMID: 15327775
  28. A novel ES cell line, TT2, with high germline-differentiating potency.
    Anal Biochem. 1993 Oct;214(1):70-6 PMID: 8250257
  29. Crystal structure of the nucleosome core particle at 2.8 A resolution.
    Nature. 1997 Sep 18;389(6648):251-60 PMID: 9305837
  30. Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31.
    EMBO J. 1999 Apr 1;18(7):1923-38 PMID: 10202156
  31. The language of covalent histone modifications.
    Nature. 2000 Jan 6;403(6765):41-5 PMID: 10638745
  32. The HP1 protein family: getting a grip on chromatin.
    Curr Opin Genet Dev. 2000 Apr;10(2):204-10 PMID: 10753776
  33. Regulation of chromatin structure by site-specific histone H3 methyltransferases.
    Nature. 2000 Aug 10;406(6796):593-9 PMID: 10949293
  34. Histone acetylation and an epigenetic code.
    Bioessays. 2000 Sep;22(9):836-45 PMID: 10944586
  35. Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression.
    Mol Cell Biol. 2000 Dec;20(24):9423-33 PMID: 11094092
  36. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
    Nature. 2001 Mar 1;410(6824):116-20 PMID: 11242053
  37. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
    Nature. 2001 Mar 1;410(6824):120-4 PMID: 11242054
  38. 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 Jul 6;276(27):25309-17 PMID: 11316813
  39. Translating the histone code.
    Science. 2001 Aug 10;293(5532):1074-80 PMID: 11498575
  40. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis.
    Genes Dev. 2002 Jul 15;16(14):1779-91 PMID: 12130538
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1284005
Published
2005-04-01
Epub
2005-00-17
Pages
815-26
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1074319
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1284005 PMC Full Text View journal details
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