RRC ID 29142
Author Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H, Shinkai Y.
Title G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis.
Journal Genes Dev
Abstract Covalent modification of histone tails is crucial for transcriptional regulation, mitotic chromosomal condensation, and heterochromatin formation. Histone H3 lysine 9 (H3-K9) methylation catalyzed by the Suv39h family proteins is essential for establishing the architecture of pericentric heterochromatin. We recently identified a mammalian histone methyltransferase (HMTase), G9a, which has strong HMTase activity towards H3-K9 in vitro. To investigate the in vivo functions of G9a, we generated G9a-deficient mice and embryonic stem (ES) cells. We found that H3-K9 methylation was drastically decreased in G9a-deficient embryos, which displayed severe growth retardation and early lethality. G9a-deficient ES cells also exhibited reduced H3-K9 methylation compared to wild-type cells, indicating that G9a is a dominant H3-K9 HMTase in vivo. Importantly, the loss of G9a abolished methylated H3-K9 mostly in euchromatic regions. Finally, G9a exerted a transcriptionally suppressive function that depended on its HMTase activity. Our results indicate that euchromatic H3-K9 methylation regulated by G9a is essential for early embryogenesis and is involved in the transcriptional repression of developmental genes.
Volume 16(14)
Pages 1779-91
Published 2002-7-15
DOI 10.1101/gad.989402
PMID 12130538
PMC PMC186403
MeSH Acetylation Animals Embryonic and Fetal Development Euchromatin / metabolism* Gene Targeting Germ Cells Histone Methyltransferases Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism* Histones / metabolism* Lysine / metabolism* Methylation Methyltransferases / genetics Methyltransferases / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Protein Methyltransferases Repressor Proteins / genetics Repressor Proteins / metabolism* Transcription, Genetic
IF 9.527
Times Cited 795
WOS Category GENETICS & HEREDITY DEVELOPMENTAL BIOLOGY CELL BIOLOGY
Resource
DNA material pZErO-2.1 mG9a-S (RDB05727) pZErO-2.1 mG9a-L (RDB05728)