G9a is a histone methyltransferase that is specific to lysine 9 of histone H3 (H3K9). Methylation of H3K9 is a signal of transcriptional repression. Recombinant G9a protein (accession number NP_006700.3) was expressed in Sf9 cells and contains an N-terminal FLAG tag with a molecular weight of 134 kDa.
G9a, also known as Euchromatic Histone-lysine N-methyltransferase 2 (EHMT2), is a histone methyltransferase that specifically mono- and dimethylates Lys9 of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by initiating recruitment of HP1 proteins to methylated histones. G9a also mediates monomethylation of Lys56 of histone H3 (H3K56me1) in G1 phase and regulates DNA replication by promoting the interaction between histone H3 and PCNA. G9a also weakly methylates Lys27 of histone H3 (H3K27me). In addition, G9a is required for DNA methylation. However, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. G9a is most likely targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. G9a may also methylate histone H1. In addition to histone methyltransferase activity, G9a also methylates non-histone proteins. It has been shown to mediate dimethylation of Lys373 of p53 and also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.