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

Abstract

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.

PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis

“…Histone H3 lysine 9 dimethylation (H3K9me2) is an important epigenetic modification mainly localized within the silent regions of the euchromatin and associated with transcriptional silencing [6][7][8][9]. Three methyltransferases G9a, GLP-1 (EuHMTare), and ESET (SetDB1) have been identified to be able to catalyze the formation of H3K9me2 [8,[10][11][12][13], and G9a is a major histone methyltransferase for H3K9me2, because knockout of this gene in mice causes a 90% loss of H3K9me2 [6,7,9].…”

Messenger RNA expression patterns of histone‐associated genes in bovine preimplantation embryos derived from different origins

“…Histone methyltransferases (HMTs) transfer methyl groups to the lysine residues of the chromatin envelope, resulting in mono-, di-, or trimethylated lysine correlating with different chromatin regions (Zhang and Reinberg, 2001;Rice et al, 2003). The histone lysine methyltransferases SUV39H1 and G9A are SET domain-containing proteins that catalyze H3-K9 methylation (Tachibana et al, 2001(Tachibana et al, , 2002. SUV39H1 mediates trimethylation of histone 3/lysine 9 that are enriched within pericentric heterochromatin, while the G9A methyltransferase is required for lysine 9 mono-and dimethylation in histone 3 and marks silent euchromatic regions (Lehnertz et al, 2003;Rice et al, 2003).…”

Histone methyltransferase G9a contributes to H3K27 methylation in vivo

“…On the other hand, G9a is a histone methyltransferase that controls H3K9me2 in vivo and predominantly represses genes at euchromatic regions [4]. It has also been reported to act on H3K27 in vitro on H3 tail fused with a GST tag [5], but its role in H3K27 methylation has not been tested on the nucleosomes, the native substrates for histone methyltransferases. In addition, G9a's contribution to H3K27 methylation in vivo remains obscure.…”