title: Characterization of a lysine-specific histone demethylase from Arabidopsis thaliana.
abstract: Arabidopsis thaliana has four genes with close homology to human histone H3 lysine 4 demethylase (HsLSD1), a component of various transcriptional corepressor complexes that often also contain histone deacetylases and the corepressor protein CoREST. All four Arabidopsis proteins contain a flavin amine oxidase domain and a SWIRM domain, the latter being present in a number of proteins involved in chromatin regulation. Here, we describe the heterologous expression and biochemical characterization of one of these Arabidopsis proteins (AtLSD1) and show that, similarly to HsLSD1, it has demethylase activity toward mono- and dimethylated Lys4 but not dimethylated Lys9 and Lys27 of histone 3. Modeling of the AtLSD1 three-dimensional structure using the HsLSD1 crystal structure as a template revealed a high degree of conservation of the residues building up the active site and some important differences. Among these differences, the most prominent is the lack of the HsLSD1 Tower domain, which has been shown to interact with CoREST and to be indispensable for HsLSD1 demethylase activity. This observation, together with AtLSD1 peculiar surface electrostatic potential distribution, suggests that the molecular partners of AtLSD1 are probably different from those of the human orthologue.
authors.affiliation: Department of Biology, University Roma Tre, 00146 Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Spedaletti
authors.forename: Fabio
authors.initials: F
authors.lastname: Polticelli
authors.forename: Viviana
authors.initials: V
authors.lastname: Capodaglio
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Schininà
authors.forename: Pasquale
authors.initials: P
authors.lastname: Stano
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Federico
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Tavladoraki
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics; D001665:Binding Sites; D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D018506:Gene Expression Regulation, Plant; D018745:Genome, Plant; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D006657:Histones; D010089:Oxidoreductases, N-Demethylating; D008239:Lysine