title: 8 Demethylation pathways for histone methyllysine residues.
abstract: Histone lysine methylation is one of the posttranslational modifications involved in transcriptional regulation and chromatin remodeling. The first lysine specific histone demethylase (LSD1) has been recently discovered, whichrules out the hypothesis that histone methylation represents a permanent epigenetic mark. LSD1 (previously known as KIAA0601) has been typically found in association with CoREST (a corepressor protein) and histone deacetylases 1 and 2, forming a highly conserved core complex. These proteins have been shown to be part of several megadalton corepressor complexes, which are proposed to operate in the context of a stable and extended form of repression through silencing of entire chromatin domains. LSD1 is a FAD-dependent protein that specifically catalyzes the demethylation of Lys4 of histone H3 by an oxidative process. The amino acid sequence of the human enzyme (90 kDa) has a modular organization with an N-terminal SWIRM domain, which has been found to mediate protein-protein interactions, and a C-terminal domain similar to FAD-dependent amine oxidases. Three assays based on different events of the demethylation reaction can be used to study LSD1 biochemical properties. The strict substrate specificity of LSD1 suggests the existence of other putative histone lysine demethylases that may use alternative mechanisms for the regulation of this posttranslational modification.
authors.affiliation: Dipartimento di Genetica e Microbiologia Università di Pavia Via Ferrata 1 Pavia 27100, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Forneris
authors.affiliation: Dipartimento di Genetica e Microbiologia Università di Pavia Via Ferrata 1 Pavia 27100, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Binda
authors.affiliation: Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano Via Celoria 26 Milano 20133, Italy.
authors.forename: MariaAntonietta
authors.initials: M
authors.lastname: Vanoni
authors.affiliation: Dipartimento di Genetica e Microbiologia Università di Pavia Via Ferrata 1 Pavia 27100, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mattevi
authors.affiliation: Dipartimento di Biologia e Genetica per le Scienze Mediche Università di Milano Via Celoria 26 Milano 20133, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Battagliol