EHMT2


Description

The EHMT2 (euchromatic histone lysine methyltransferase 2) is a protein-coding gene located on chromosome 6.

Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a, is a histone methyltransferase enzyme that in humans is encoded by the EHMT2 gene. G9a deposits the mono- and di-methylated states of histone H3 at lysine residue 9 (i.e., H3K9me1 and H3K9me2) and lysine residue 27 (H3K27me1 and H3K27me2). The presence of H3K9me1/2 is usually associated with gene silencing.

A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. This gene is found near this cluster; it was mapped near the gene for C2 within a 120-kb region that included a HSP70 gene pair. These genes are all within the human major histocompatibility complex class III region. This gene was thought to be two different genes, NG36 and G9a, adjacent to each other but a recent publication shows that there is only a single gene. The protein encoded by this gene is thought to be involved in intracellular protein-protein interaction. There are three alternatively spliced transcript variants of this gene but only two are fully described. G9a and G9a-like protein, another histone-lysine N-methyltransferase, catalyze the synthesis of H3K9me2, which is a repressive mark.

EHMT2 is a histone methyltransferase that specifically mono- and dimethylates lysine 9 of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9 methylation is a mark for epigenetic transcriptional repression, as it recruits HP1 proteins to methylated histones. EHMT2 also mediates monomethylation of lysine 56 of histone H3 (H3K56me1) in G1 phase, promoting interaction between histone H3 and PCNA and regulating DNA replication. It weakly methylates lysine 27 of histone H3 (H3K27me). EHMT2 is required for DNA methylation, but its histone methyltransferase activity is not required for this process, suggesting that these two activities function independently. It is likely targeted to histone H3 by DNA-binding proteins such as E2F6, MGA, MAX, and/or DP1. EHMT2 may also methylate histone H1. In addition to its histone methyltransferase activity, EHMT2 methylates non-histone proteins, including lysine 373 of p53/TP53. EHMT2 also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12, and itself. It is recruited to the promoters of target genes through interaction with the transcriptional repressor MSX1, leading to the inhibition of myoblast differentiation by repressing the transcription of differentiation factors.

EHMT2 is also known as BAT8, C6orf30, G9A, GAT8, KMT1C, NG36.

Associated Diseases


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