RRC ID |
29142
|
著者 |
Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H, Shinkai Y.
|
タイトル |
G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis.
|
ジャーナル |
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.
|
巻・号 |
16(14)
|
ページ |
1779-91
|
公開日 |
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
|
引用数 |
795
|
WOS 分野
|
GENETICS & HEREDITY
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
リソース情報 |
遺伝子材料 |
pZErO-2.1 mG9a-S (RDB05727)
pZErO-2.1 mG9a-L (RDB05728) |