title: The Saccharomyces cerevisiae histone demethylase Jhd1 fine-tunes the distribution of H3K36me2.
abstract: Histone methylation plays important roles in the regulation of chromatin dynamics and transcription. Steady-state levels of histone lysine methylation are regulated by a balance between enzymes that catalyze either the addition or removal of methyl groups. Using an activity-based biochemical approach, we recently uncovered the JmjC domain as an evolutionarily conserved signature motif for histone demethylases. Furthermore, we demonstrated that Jhd1, a JmjC domain-containing protein in Saccharomyces cerevisiae, is an H3K36-specific demethylase. Here we report further characterization of Jhd1. Similar to its mammalian homolog, Jhd1-catalyzed histone demethylation requires iron and alpha-ketoglutarate as cofactors. Mutation and deletion studies indicate that the JmjC domain and adjacent sequences are critical for Jhd1 enzymatic activity, while the N-terminal PHD domain is dispensable. Overexpression of JHD1 results in a global reduction of H3K36 methylation in vivo. Finally, chromatin immunoprecipitation-coupled microarray studies reveal subtle changes in the distribution of H3K36me2 upon overexpression or deletion of JHD1. Our studies establish Jhd1 as a histone demethylase in budding yeast and suggest that Jhd1 functions to maintain the fidelity of histone methylation patterns along transcription units.
authors.affiliation: Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Fang
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hogan
authors.forename: Gaoyang
authors.initials: G
authors.lastname: Liang
authors.forename: Jason D
authors.initials: JD
authors.lastname: Lieb
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D017353:Gene Deletion; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000494:pharmacology; D056484:Jumonji Domain-Containing Histone Demethylases; D007656:Ketoglutaric Acids / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism*; D008745:Methylation / Q000187:drug effects; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D006657:Histones; D007656:Ketoglutaric Acids; D029701:Saccharomyces cerevisiae Proteins; D007501:Iron; C521733:Jhd1 protein, S cerevisiae; D056484:Jumonji Domain-Containing Histone Demethylases; D010089:Oxidoreductases, N-Demethylating; D008239:Lysine