Histone lysine demethylase 6B (KDM6B)

Histone lysine demethylase 6B (KDM6B), also known as JMJD3, is a JmjC domain-containing enzyme that specifically demethylates di- and tri-methylated lysine 27 on histone H3 (H3K27me2/3). This catalytic activity removes a key repressive epigenetic mark, thereby facilitating chromatin remodeling and the transcriptional activation of specific target genes involved in development, cell differentiation, and the inflammatory response (1, 2, 6). KDM6B plays a critical role in various pathologies; it is often overexpressed in numerous cancers, including glioblastoma, prostate cancer, and leukemia, where it promotes oncogenesis by derepressing genes associated with proliferation and survival (1, 6, 11). Furthermore, its involvement in the induction of pro-inflammatory cytokines makes it a significant player in chronic inflammatory and autoimmune conditions such as rheumatoid arthritis and psoriasis (1, 5, 9). Small molecule inhibitors, such as the cell-permeable prodrug GSK-J4, have been developed to block the enzymatic activity of KDM6B by competitively binding to its 2-oxoglutarate active site (5, 11, 15). These inhibitors aim to restore the repressive H3K27me3 mark on pathogenic genes, offering a promising epigenetic strategy for treating cancer and inflammatory disorders (1, 11).

Other names

JMJD3Jumonji Domain Containing 3KIAA0346Lysine (K)-specific demethylase 6B[Histone H3]-trimethyl-L-lysine(27) demethylase 6BJmjC domain-containing protein 3NEDCFSA

Small molecule inhibition of the JmjC domain by competitive binding to the 2-oxoglutarate active site, which prevents the demethylation of H3K27me2/3 marks and subsequently maintains the repression of target genes.