Histone Lysine demethylases
Histone methylation marks convey important information in terms of gene regulation. But these marks need to be exchanged time and again in order to switch gene expression as and when required. Two major types of demethylase are known:
Lysine-specific demethylase (LSD1/KDM1): They contain an amine oxidase (AO) catalytic domain that mediates oxidative demethylation of methylated lysine residues by reducing FAD molecules.
Jumonji histone demethylases: They contain the catalytic JmJC domain and may or may not contain other associated domains like JmJN, ARID, PHD, Tudor etc. Based on domain architecture and homology, they are divided into 7 groups: JHDM1, JHDM2, JHDM3/JMJD2, JARID, JMJC domain only, PHF2/PHF8 and UTX/UTY. They belong to Fe(II)/2-oxoglutarate-dependent dioxygenase (or hydroxylase) superfamily that catalyse demethylation via multiple steps using the Fe(IV)-oxo species.
Histone demethylases have important role in various cellular processes like cell cycle progression, transcriptional regulation of hox genes, nuclear hormone mediated and NF-kB signalling, p53 regulation, unperturbed mitosis, fetoplacental development, regulation of DNA replication, control of rRNA expression, DNA repair processes etc. They are also implicated in the development of various diseases and cancers like X linked mental retardation, human papilloma virus (HPV)-associated cancers, renal cancers, breast cancers, prostate cancers, blood cancers, colon cancers, brain cancers.Cytogenetic map of Lysine demethylases coding genes