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G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis
Open accessAbstract
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.
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Metadata
- Authors
- Tachibana, M., Sugimoto, K., Nozaki, M., Ueda, J., Ohta, T., Ohki, M., Fukuda, M., Takeda, N., Niida, H., Kato, H., & Shinkai, Y.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-07-15
- Volume
- 16
- Issue
- 14
- Pages
- 1779-1791
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2130350241
- Cited by
- 1,253
- References
- 5
- Type
- posted content
- Language
- en
- Open access
- diamond
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