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

AUTOR(ES)

Tachibana, Makoto

FONTE

Cold Spring Harbor Laboratory Press

RESUMO

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.

Documentos Relacionados

• Histone H3 lysine 9 methylation is required for DNA elimination in developing macronuclei in Tetrahymena
• DNA methylation controls histone H3 lysine 9 methylation and heterochromatin assembly in Arabidopsis
• Histone H3-K9 Methyltransferase ESET Is Essential for Early Development
• Parent-Specific Complementary Patterns of Histone H3 Lysine 9 and H3 Lysine 4 Methylation at the Prader-Willi Syndrome Imprinting Center
• Chromatin immunoprecipitation microarrays for identification of genes silenced by histone H3 lysine 9 methylation