G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis.
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.
Tachibana
Makoto
M
Department of Cell Biology, Institute for Virus Research, Kyoto University, Shogoin Kawara-cho, Kyoto 606-8507, Japan.
Sugimoto
Kenji
K
Nozaki
Masami
M
Ueda
Jun
J
Ohta
Tsutomu
T
Ohki
Misao
M
Fukuda
Mikiko
M
Takeda
Naoki
N
Niida
Hiroyuki
H
Kato
Hiroyuki
H
Shinkai
Yoichi
Y
D000107:Acetylation; D000818:Animals; D005314:Embryonic and Fetal Development; D022041:Euchromatin / Q000378:metabolism*; D018390:Gene Targeting; D005854:Germ Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D022041:Euchromatin; D006657:Histones; D012097:Repressor Proteins; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine