G9a，also known as Euchromatic histonelysine Nmethyltransferase 2 （EHMT2），is a member of a family of histone lysine methyltransferases. Recombinant G9a can mono，di and trimethylate histone H3 on Lys9 and Lys27 in vitro. However，in vivo G9a forms a complex with GLP，a G9arelated histone methyltransferase，and together these proteins function as the major euchromatic histone H3 Lys9 mono and dimethyltransferases，creating transcriptionally repressive marks that facilitate gene silencing. G9a methylates itself on Lys165，a modification that regulates the association of HP1 repressor proteins with the G9a/GLP complex. The G9a/GLP complex also contains Wiz，a zinc finger protein that is required for G9a/GLP heterodimerization and complex stability. Wiz contains two CtBP corepressor binding sites，which mediate the association of the G9a/GLP with the CtBP corepressor complex. In addition，G9a and GLP are components of other large transcriptional corepressor complexes，such as those involving E2F6 and CDP/cut. G9a interacts with DNMT1，and both proteins are required for methylation of DNA and histone H3 （Lys9） at replication foci，providing a functional link between histone H3 Lys9 and CpG methylation during DNA replication. G9a activity is critical for meiotic prophase progression，as mutant mice deficient in germ line G9a show a large loss of mature gametes. In addition，G9a facilitates increased global levels of dimethyl histone H3 （Lys9） during hypoxic stress and increased G9a expression is associated with hepatocellular carcinoma.
