RRC ID 28670
Author Tachibana M, Ueda J, Fukuda M, Takeda N, Ohta T, Iwanari H, Sakihama T, Kodama T, Hamakubo T, Shinkai Y.
Title Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9.
Journal Genes Dev
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.
Volume 19(7)
Pages 815-26
Published 2005-4-1
DOI 10.1101/gad.1284005
PII gad.1284005
PMID 15774718
PMC PMC1074319
MeSH Animals Euchromatin / enzymology* Histone Methyltransferases Histone-Lysine N-Methyltransferase / chemistry* Histone-Lysine N-Methyltransferase / metabolism Histones / metabolism* Lysine / metabolism* Methylation Mice Protein Methyltransferases Protein Structure, Quaternary Stem Cells / enzymology
IF 9.527
Times Cited 493
DNA material 14-1 (RDB05729)