Histone Demethylases

Supporting information

Histone demethylases (KDMs) are a family of enzymes that catalyze the removal of methyl groups from lysine and arginine residues on histone tails. They reverse the methylation of lysine and arginine residues that is catalyzed by histone methyltransferases.

The first histone demethylase to be discovered was lysine-specific demethylase 1 (LSD1), but further research identified an additional family of histone demethylases; the Jumonji C domain-containing demethylases (JMJD). JMJDs require both Fe2+ and 2-oxoglutarate as co-factors for histone demethylation, whilst the catalysis carried out by LSD1 is dependent on the presence of a protonated nitrogen atom. The JMJD family of demethylases remove methyl groups from tri-methylated histone arginine and lysine residues whereas LSD1 demethylates mono- and di-methylated lysine residues on histone H3 (H3K4 and H3K9), but cannot demethylate tri-methylated residues. To date, only one member of the JMJD family - JMJD6 - has been shown to specifically demethylate arginine residues.

The removal of methyl groups from histone lysine and arginine residues is typically associated with transcriptional repression, but this is not true in all cases; the histone demethylase JMJD2A has recently been shown to function as a transcriptional co-activator of androgen receptor responsive genes.

In addition to co-activation of androgen receptor responsive genes, the biological functions of JMJDs include stem cell self-renewal, the inflammatory response and cell differentiation. JMJD1A has also been shown to be essential during spermatogenesis. LSD1 is also involved in a wide array of biological processes including cell proliferation, chromosome segregation and embryonic development, but more recently has been identified as a potential target for cancer therapeutics.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
KDM1A Human KDM1A NM_015013 O60341
Mouse Kdm1a NM_133872 Q6ZQ88
Rat Kdm1a NM_001130098 NP_001123570
KDM1B Human KDM1B NM_153042 Q8NB78
Mouse Kdm1b NM_172262 Q8CIG3
Rat Kdm1b NM_001107343 NP_001100813
View all Histone Demethylase Gene Data »

Literature for Histone Demethylases

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