title: Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9.
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.
authors.affiliation: Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tachibana
authors.forename: Jun
authors.initials: J
authors.lastname: Ueda
authors.forename: Mikiko
authors.initials: M
authors.lastname: Fukuda
authors.forename: Naoki
authors.initials: N
authors.lastname: Takeda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ohta
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.forename: Toshiko
authors.initials: T
authors.lastname: Sakihama
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
mesh_terms: D000818:Animals; D022041:Euchromatin / Q000201:enzymology*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D011496:Protein Methyltransferases; D020836:Protein Structure, Quaternary; D013234:Stem Cells / Q000201:enzymology
chemical_list: D022041:Euchromatin; D006657:Histones; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; C513479:GLP protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine