Reaction: a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2 (overall reaction)
(1a) a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
(1b) a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2 = a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
Other name(s): KDM3A (gene name); KDM3B (gene name); JMJD1A (gene name); JMJD1B (gene name); JHDM2A (gene name); JHDM2B (gene name); KDM7B (gene name); PHF8 (gene name); HR (gene name)
Systematic name: [histone H3]-N6,N6-dimethyl-L-lysine-9,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys-9 residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the di- and mono-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.66, [histone H3]-trimethyl-L-lysine9 demethylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J. and Zhang, Y. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell 125 (2006) 483-495. [PMID: 16603237]
2. Loh, Y.H., Zhang, W., Chen, X., George, J. and Ng, H.H. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 21 (2007) 2545-2557. [PMID: 17938240]
3. Feng, W., Yonezawa, M., Ye, J., Jenuwein, T. and Grummt, I. PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation. Nat. Struct. Mol. Biol. 17 (2010) 445-450. [PMID: 20208542]
4. Kuroki, S., Matoba, S., Akiyoshi, M., Matsumura, Y., Miyachi, H., Mise, N., Abe, K., Ogura, A., Wilhelm, D., Koopman, P., Nozaki, M., Kanai, Y., Shinkai, Y. and Tachibana, M. Epigenetic regulation of mouse sex determination by the histone demethylase Jmjd1a. Science 341 (2013) 1106-1109. [PMID: 24009392]
5. Liu, L., Kim, H., Casta, A., Kobayashi, Y., Shapiro, L.S. and Christiano, A.M. Hairless is a histone H3K9 demethylase. FASEB J. 28 (2014) 1534-1542. [PMID: 24334705]