| Title | A novel mammalian flavin-dependent histone demethylase. | | Author(s) | Karytinos A, Forneris F, Profumo A, Ciossani G, Battaglioli E, Binda C, Mattevi A | | Institution | Dept. Genetics and Microbiology, University of Pavia, Italy; | | Source | J Biol Chem 2009 Apr 30. | | Abstract | Methylation of Lys residues on histone proteins is a well-known and extensively characterized epigenetic mark. The recent discovery of Lysine-Specific Demethylase 1 (LSD1) demonstrated that lysine methylation can be dynamically controlled. Among the histone demethylases so far identified, LSD1 has the unique feature of functioning through a flavin-dependent amine oxidation reaction. Database analysis reveals that mammalian genomes contain a gene (AOF1, amine-oxidase flavin-containing domain 1) which is homologous to the LSD1-coding gene. Here, we demonstrate that the protein encoded by AOF1 represents a second mammalian flavin-dependent histone demethylase, named LSD2. The new demethylase is strictly specific for mono- and di-methylated Lys4 of histone H3, recognizes a long stretch of the H3 N-terminal tail, senses the presence of additional epigenetic marks on the histone substrate, and is covalently inhibited by tranylcypromine. As opposed to LSD1, LSD2 does not form a biochemically stable complex with the C-terminal domain of the corepressor protein CoREST. Furthermore, LSD2 contains a CW-type zinc-finger motif with potential zinc-binding sites, which are not present in LSD1. We conclude that mammalian LSD2 represents a new flavin-dependent H3-Lys4 demethylase, which features substrate-specificity properties highly similar to those of LSD1 but is very likely to be part of chromatin-remodeling complexes that are distinct from those involving LSD1. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19407342 |
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