title: Splicing regulates NAD metabolite binding to histone macroH2A.
abstract: Histone macroH2A is a hallmark of mammalian heterochromatin. Here we show that human macroH2A1.1 binds the SirT1-metabolite O-acetyl-ADP-ribose (OAADPR) through its macro domain. The 1.6-A crystal structure and mutants reveal how the metabolite is recognized. Mutually exclusive exon use in the gene H2AFY produces macroH2A1.2, whose tissue distribution differs. MacroH2A1.2 shows only subtle structural changes but cannot bind nucleotides. Alternative splicing may thus regulate the binding of nicotinamide adenine dinucleotide (NAD) metabolites to chromatin.
authors.affiliation: Gene Expression Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Kustatscher
authors.forename: Michael
authors.initials: M
authors.lastname: Hothorn
authors.forename: Céline
authors.initials: C
authors.lastname: Pugieux
authors.forename: Klaus
authors.initials: K
authors.lastname: Scheffzek
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Ladurner
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D003461:Crystallography; D040461:Gene Components; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D038961:O-Acetyl-ADP-Ribose / Q000737:chemistry / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D006657:Histones; D038961:O-Acetyl-ADP-Ribose; C120756:macroH2A histone; D009243:NAD; D037761:Sirtuins