Reactome | KDM1A, KDM1B demethylate MeK5-histone H3

KDM1A, KDM1B demethylate MeK5-histone H3

Stable Identifier

R-HSA-3214912

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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KDM1A, KDM1B demethylate MeK5-histone H3

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Histone demethylases (HDMs) belong to two groups with distinct catalytic mechanisms. KDM1A and KDM1B (formerly known as Lysine Specific Demethylases 1 and 2), belong to the flavin adenine dinucleotide (FAD)-dependent amino oxidase family, releasing formaldehyde. The reaction mechanism requires a protonatable lysine epsilon-amino group, not available in trimethylated lysines (Shi et al. 2004). KDM1A and subsequently KDM1B were shown to catalyse demethylation of monomethyl and dimethyl, but not trimethyl, histone H3 at lysine 5 (H3K4) in vitro (Shi et al. 2004, Ciccone et al. 2009).
Subsequently KDM1A was found to be much more proficient at catalysing demethylation of H3K4 when part of a multiprotein complex (Lee et al. 2005) and shown to catalyse demethylation of histone H3 at lysine 10 (H3K9) in vivo when associated with the androgen receptor (Metzger et al. 2007), suggesting that its substrate specificity is modulated by interacting proteins. KDM1A is a subunit of several complexes, including CtBP, Co-REST, NRD and BRAF35 (Lan et al. 2008). It is also able to catalyse demethylation of a number of non-histone proteins (Nicholson & Chen 2009).

Literature References

PubMed ID	Title	Journal	Year
15620353	Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 Mulligan, P, Matson, C, Shi, Y, Cole, PA, Lan, F, Shi, Y, Casero, RA, Whetstine, JR	Cell	2004
19727073	KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints Chen, T, Bajko, J, Xu, G, Gay, F, Lei, H, Su, H, Li, E, Ciccone, DN, Hevi, S	Nature	2009