G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis (original) (raw)
- Makoto Tachibana1,
- Kenji Sugimoto2,
- Masami Nozaki3,
- Jun Ueda1,
- Tsutomu Ohta4,
- Misao Ohki4,
- Mikiko Fukuda1,
- Naoki Takeda5,7,
- Hiroyuki Niida5,8,
- Hiroyuki Kato6, and
- Yoichi Shinkai1,9
- 1Department of Cell Biology, Institute for Virus Research, Kyoto University, Shogoin Kawara-cho, Kyoto 606-8507, Japan;2Laboratory of Applied Molecular Biology, Department of Applied Biochemistry, Osaka Prefecture University, Osaka 599-8501, Japan; 3Research Institute for Microbial Disease, Osaka University, Osaka 565-0871, Japan; 4Medical Genomics Center, National Cancer Center Research Institute, Tokyo 104-0045, Japan;5Department of Oncology, Nippon Roche Research Center, Kamakura 247-0063, Japan; 6National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan
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.
- Euchromatin
- heterochromatin
- histone H3-K9 methylation
- G9a HMTase
- mammalian development
- transcriptional regulation
Footnotes
Present addresses: 7Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan;8Department of Biochemistry, Nagoya City University Medical School, Nagoya 467-8601, Japan.
↵9 Corresponding author.
E-MAIL yshinkai{at}virus.kyoto-u.ac.jp; FAX 81-75-751-3991.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.989402.
- Received March 5, 2002.
- Accepted May 22, 2002.
Cold Spring Harbor Laboratory Press