G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis

• Published in: Genes & development Vol. 16; no. 14; pp. 1779 - 1791
• Main Authors: Tachibana, Makoto, Sugimoto, Kenji, Nozaki, Masami, Ueda, Jun, Ohta, Tsutomu, Ohki, Misao, Fukuda, Mikiko, Takeda, Naoki, Niida, Hiroyuki, Kato, Hiroyuki, Shinkai, Yoichi
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 15.07.2002
• Subjects: Acetylation; Animals; Embryonic and Fetal Development; Euchromatin - metabolism; Gene Targeting; Germ Cells; 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; Research Paper; Transcription, Genetic
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.989402

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.