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

By M. Tachibana, K. Sugimoto, M. Nozaki, Jun Ueda, T. Ohta, M. Ohki, Mikiko Fukuda, N. Takeda, Hiroyuki Niida, H. Kato and 1 more. Genes & Development, 2002

1,277 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8b50a1e1f2910e13ad3b04518e3fd9c28ca38bae

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Citations in the corpus

• Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. (2003, methodology): “, 2003), and G9a-deficient mouse embryonic stem (ES) cells (Tachibana et al., 2002) was done as described TGACGAAATC-3 and (MajR1) 5 -CATATTCCAGGTCCTT-CAGTG”
• G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis (2006, background): “For reversal experiments, wild-type, G9a –/– (clones 10–20, 2–3) and G9a –/– Tg ES cells, as well as Dnmt3a / 3b –/–15,19 , were induced to differentiate with 1 µ M 1d). bp, base pairs.”
• Enhanced expression of EHMT2 is involved in the proliferation of cancer cells through negative regulation of SIAH1. (2011, background): “Knockout of EHMT2 causes embryonic lethality in mice, indicating a major role for epigenetic repression in early mammalian development [12].”
• JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. (2006, methodology): “When the G9a-methylated histone substrates were subjected to demethylation assays using the protein fractions derived from HeLa nuclear extracts (NE) and nuclear pellet (NP; Wang et al., 2001b), we detected a potential H3K9 demethylase activity in the nuclear extract-derived 0.3 M P11 protein fracti”
• Distinct Epigenomic Landscapes of Pluripotent and Lineage-committed Human Cells (2010, background): “Knockout studies of H3K9 methyltransferases and H3K27 methyltransferases lead to differentiation or developmental defects (Dodge et al., 2004; Faust et al., 1998; O’Carroll et al., 2001; Pasini et al., 2007; Peters et al., 2001; Tachibana et al., 2002), suggesting that epigenetic mechanisms play a c”
• Epigenetic reprogramming in mammals. (2005, background): “The early appearance of histone methylation marks implies that histone residues are rapidly deacteylated and then monomethylated by the appropriate histone methyltransferases (HMTases): SET 7/9 for H3K4me (43), G9a and ESET for H3K9me (44,45) and an unknown HMTase for H3K27me independent of Ezh2 (de”
• Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. (2002, background): “In vivo, however, G9a clearly targets H3-K9; whether or not the extent of H3-K27 methylation is decreased in G9anull cells is unknown (Tachibana et al. 2002).”
• How do lncRNAs regulate transcription? (2017, background): “Its essential role is highlighted by lethality and severe growth defects observed in G9a-deficient embryos (70).”
• How is pluripotency determined and maintained? (2007, background): “5 NT Normal Normal Defective Restored Lei et al., 1996; Gaudet et al., 1998 Dnmt3a/3b Die at E11.”
• An epigenetic road map for histone lysine methylation (2003, background): “Recruitment of several H3-K9-specific HMTases induces gene repression within euchromatin (Tachibana et al., 2001; Nielsen et al., 2001; Vandel et al., 2001; Ogawa et al., 2002; Schultz et al., 2002; Tachibana et al., 2002; Yang et al., 2002).”