Article
- The EMBO Journal (2008) 27, 2681 - 2690
- doi:10.1038/emboj.2008.192
Published online: 25 September 2008
Subject Category:
G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription
Makoto Tachibana1,2, Yasuko Matsumura1, Mikiko Fukuda1, Hiroshi Kimura3 and Yoichi Shinkai1,2
- Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, Japan
- Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan
- Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan
Correspondence to:
Makoto Tachibana, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. Tel.:+81 75 751 3991; Fax: +81 75 751 3991; E-mail: mtachiba@virus.kyoto-u.ac.jp
Yoichi Shinkai, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. Tel.:+81 75 751 3991; Fax: +81 75 751 3991; E-mail: yshinkai@virus.kyoto-u.ac.jp
Received 2 April 2008; Accepted 27 August 2008
Abstract
Methylation of DNA and lysine 9 of histone H3 (H3K9) are well-conserved epigenetic marks for transcriptional silencing. Although H3K9 methylation directs DNA methylation in filamentous fungi and plants, this pathway has not been corroborated in mammals. G9a and GLP/Eu-HMTase1 are two-related mammalian lysine methyltransferases and a G9a/GLP heteromeric complex regulates H3K9 methylation of euchromatin. To elucidate the function of G9a/GLP-mediated H3K9 methylation in the regulation of DNA methylation and transcriptional silencing, we characterized ES cells expressing catalytically inactive mutants of G9a and/or GLP. Interestingly, in ES cells expressing a G9a-mutant/GLP complex that does not rescue global H3K9 methylation, G9a/GLP-target genes remain silent. The CpG sites of the promoter regions of these genes were hypermethylated in such mutant ES cells, but hypomethylated in G9a- or GLP-KO ES cells. Treatment with a DNA methyltransferase inhibitor reactivates these G9a/GLP-target genes in ES cells expressing catalytically inactive G9a/GLP proteins, but not the wild-type proteins. This is the first clear evidence that G9a/GLP suppresses transcription by independently inducing both H3K9 and DNA methylation.
Keywords:
- DNA methylation,
- G9a,
- GLP,
- histone lysine methylation
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Linking DNA methylation and histone modification: patterns and paradigms
Nature Reviews Genetics Review (01 May 2009)
NEWS AND VIEWS
A gateway to study protein lysine methylation
Nature Chemical Biology News and Views (01 Jun 2008)
RESEARCH
DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity
The EMBO Journal Article (22 Oct 2008)
De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes
Nature Structural & Molecular Biology Article (01 Nov 2008)
Epigenetic regulation of X-linked cancer/germline antigen genes by DNMT1 and DNMT3b
Oncogene Original Article
