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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.

Pubmed ID: 12130538

Authors

  • Tachibana M
  • Sugimoto K
  • Nozaki M
  • Ueda J
  • Ohta T
  • Ohki M
  • Fukuda M
  • Takeda N
  • Niida H
  • Kato H
  • Shinkai Y

Journal

Genes & development

Publication Data

July 15, 2002

Associated Grants

None

Mesh Terms

  • Acetylation
  • Animals
  • Embryonic and Fetal Development
  • Euchromatin
  • Gene Targeting
  • Germ Cells
  • Histone-Lysine N-Methyltransferase
  • Histones
  • Lysine
  • Methylation
  • Methyltransferases
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Methyltransferases
  • Repressor Proteins
  • Transcription, Genetic