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

Genes and Development - Tập 19 Số 7 - Trang 815-826 - 2005
Makoto Tachibana1, Jun Ueda1, Mikiko Fukuda1, Naoki Takeda2, Tsutomu Ohta3, Hiroko Iwanari4, Toshiko Sakihama4, Tatsuhiko Kodama4, Takao Hamakubo4, Yoichi Shinkai1
1Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan;
2Center for Animal Resources and Development, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan;
3Center for Medical Genomics, National Cancer Center Research Institute, Chuo, Tokyo 104-0045, Japan;
4Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro, Tokyo 153-8904, Japan

Tóm tắt

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.

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Genes and Development

Tập 19 Số 7

815-826

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