Histone-lysine N-methyltransferase SETDB2 (SETDB2)

Histone-lysine N-methyltransferase SETDB2 (SETDB2) is an enzyme that catalyzes the trimethylation of histone H3 at lysine 9 (H3K9me3), a modification associated with epigenetic gene repression. SETDB2 contains both a methyl-CpG-binding domain (MBD) and a bifurcated SET domain, and is recruited to heterochromatin regions where it regulates chromosome condensation and segregation, as well as transcriptional silencing of specific genes. SETDB2 plays vital roles in embryonic development, innate and adaptive immune regulation, resolution of inflammation, and hepatic lipid metabolism. Overexpression of SETDB2 drives transcriptional silencing of tumor suppressor genes and is associated with proliferation and progression of specific cancers, notably gastric cancer. Conversely, deficiency of SETDB2 promotes vascular inflammation and atherosclerosis in mice, underscoring its role as a modulator of inflammation and immune responses[1][2][3][4][5]. Currently, there are no approved drugs specifically targeting SETDB2, but it is a member of a protein family investigated as epigenetic therapeutic targets.

Other names

C13orf4CLLD8KMT1FCLLL8SET domain bifurcated 2Chronic lymphocytic leukemia deletion region gene 8 proteinLysine N-methyltransferase 1F

Histone H3K9 methylation leading to transcriptional silencing of target genes; Recruitment of heterochromatin protein 1 (HP1) through trimethylation of H3K9; Modulation of proinflammatory gene expression and resolution of inflammation by methyl transfer to histone proteins in gene promoter regions[1][3][4]