SET Domain-containing Protein, G9a, Is a Novel Lysine-preferring Mammalian Histone Methyltransferase with Hyperactivity and Specific Selectivity to Lysines 9 and 27 of Histone H3*

By M. Tachibana, K. Sugimoto, T. Fukushima, Y. Shinkai. Journal of Biological Chemistry, 2001

795 citations recorded by the source corpus.

The covalent modification of histone tails has regulatory roles in various nuclear processes, such as control of transcription and mitotic chromosome condensation. Among the different groups of enzymes known to catalyze the covalent modification, the most recent additions are the histone methyltransferases (HMTases), whose functions are now being characterized. Here we show that a SET domain-containing protein, G9a, is a novel mammalian lysine-preferring HMTase. Like Suv39 h1, the first identified lysine-preferring mammalian HMTase, G9a transfers methyl groups to the lysine residues of histone H3, but with a 10–20-fold higher activity. It was reported that lysines 4, 9, and 27 in H3 are methylated in mammalian cells. G9a was able to add methyl groups to lysine 27 as well as 9 in H3, compared with Suv39 h1, which was only able to methylate lysine 9. Our data clearly demonstrated that G9a has an enzymatic nature distinct from Suv39 h1 and its homologue h2. Finally, fluorescent protein-labeled G9a was shown to be localized in the nucleus but not in the repressive chromatin domains of centromeric loci, in which Suv39 h1 family proteins were localized. This finding indicates that G9a may contribute to the organization of the higher order chromatin structure of non-centromeric loci.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/79713fb325f0aea6831e0688f4ad46debab3a18b

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In Molecular Biology

1. Ryuji Hamamoto
2. Yusuke Nakamura
3. Yi Zhang
4. D. Reinberg
5. C. D. Allis
6. Yang Shi
7. T. Jenuwein
8. N. Dohmae

Citations in the corpus

• EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. (2008, background): “It was reported that G9a, the HMTase catalyzing methylation on H3K9, might mediate H3K27 methylation (Tachibana et al., 2001).”
• Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. (2003, methodology): “The G9a HMTase has also been reported to be able to methylate H3-K27 in vitro (Tachibana et al., 2001) (data not shown).”
• 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).”
• Regulation of p53 activity through lysine methylation (2004, methodology): “Methods Constructs GST-H3 N-terminal peptide was expressed as describe”
• From silencing to gene expression: real-time analysis in single cells. (2004, methodology): “Images were acquired (Tachibana et al., 2001, 2002).”
• SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. (2002, background): “Alternatively, it may be that H3-K9 methylation by SETDB1 plays a role in gene-specific targeting of DNA methylation, based on a recent genetic study in Neurospora crassa that has linked maintenance of genomic DNA methylation to histone H3-K9 methylation (Tamaru and Selker 2001).”
• SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells (2004, background): “, whereas G9a functions as a 'dual' methyltransferase, catalysing histone H3-K9 and H3-K27 (ref”
• Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. (2001, background): “…methyl mark seems counter-intuitive and might be addressed, at least in part, by the existence of a histone code, wherein additional posttranslational marks on the same or different histone tail(s) could be read as either a repression or activation cassette (Strahl and Allis 2000; Turner 2000).”
• DNA methylation: superior or subordinate in the epigenetic hierarchy? (2011, background): “G9A, another histone methylase, catalyzes monomethylation and dimethylation of H3K9(29,30) and, to a lesser extent, H3K27.(29) Genome-wide DNA methylation analysis of G9a knockout murine cells reveals that it site-selectively contributes to DNA methylation.”