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.

Further reading: PMID: 17342184, PMID: 16983801, PMID: 18603028, PMID: 18722564.

Cytogenetic map of Lysine demethylases coding genes
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Different histone Lysine demethylases
Enzyme (UniprotKB recommended name) Coding gene/s Site of histone modification
Histone lysine demethylase PHF8PHF8H3K9me2, H3K4me3, H4K20me1, H3K27me2
Lysine-specific demethylase 2AKDM2AH3K36me2
Lysine-specific demethylase 2BKDM2BH3K4me3, H3K36me2
Lysine-specific demethylase 3AKDM3AH3K9me1, H3K9me2
Lysine-specific demethylase 3BKDM3BH3K9me1, H3K9me2
Lysine-specific demethylase 4AKDM4AH3K9me3, H3K36me3
Lysine-specific demethylase 4BKDM4BH3K9me3
Lysine-specific demethylase 4CKDM4CH3K9me2, H3K9me3
Lysine-specific demethylase 4DKDM4DH3K9me3, H3K9me2, H1K25me1
Lysine-specific demethylase 5AKDM5AH3K4me2, H3K4me3
Lysine-specific demethylase 5BKDM5BH3K4me3
Lysine-specific demethylase 5CKDM5CH3K4me3
Lysine-specific demethylase 5DKDM5DH3K4me3, H3K4me2
Lysine-specific demethylase 6AKDM6AH3K27me3
Lysine-specific demethylase 6BKDM6BH3K27me3, H3K27me2
Lysine-specific demethylase 7JHDM1DH3K9me2, H3K27me2
Lysine-specific demethylase 8JMJD5H3K36me2
Lysine-specific demethylase NO66C14orf169H3K4me3, H3K36me3
Lysine-specific histone demethylase 1AKDM1AH3K4me1, H3K4me2, H3K9me1, H3K9me2
Lysine-specific histone demethylase 1BKDM1BH3K9me2