Histone demethylation catalysed by LSD1 is a flavin-dependent oxidative process

• Published in: FEBS letters 2005-04, Vol.579 (10), p.2203-2207
• Main Authors: Forneris, Federico, Binda, Claudia, Vanoni, Maria Antonietta, Mattevi, Andrea, Battaglioli, Elena
• Format: Article
• Language: English
• Subjects: Amine oxidase; Catalysis; Chromatin remodelling; Flavins - metabolism; Flavoenzyme; H3-K4, Lys4 of histone 3; H3-K9, Lys9 of histone 3; Histone Demethylases; Histone methylation; Histones - metabolism; human LSD1 mutant harbouring a deletion of the N-terminal 184 amino acids; KIAA0601; LSD; Lysine - metabolism; lysine-specific histone demethylase; Methylation; Oxidation-Reduction; Oxidoreductases, N-Demethylating - metabolism; Substrate Specificity; Δ157, mutant harbouring a deletion of the N-terminal 157 amino acids; Δ184
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.03.015

Lysine-specific histone demethylase 1 (LSD1) is a very recently discovered enzyme which specifically removes methyl groups from Lys4 of histone 3. We have addressed the functional properties of the protein demonstrating that histone demethylation involves the flavin-catalysed oxidation of the methylated lysine. The nature of the substrate that acts as the electron acceptor required to complete the catalytic cycle was investigated. LSD1 converts oxygen to hydrogen peroxide although this reactivity is not as pronounced as that of other flavin-dependent oxidases. Our findings raise the possibility that in vivo LSD1 might not necessarily function as an oxidase, but it might use alternative electron acceptors.