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.