title: Histone H3 Serine 28 Is Essential for Efficient Polycomb-Mediated Gene Repression in Drosophila.
abstract: Trimethylation at histone H3K27 is central to the polycomb repression system. Juxtaposed to H3K27 is a widely conserved phosphorylatable serine residue (H3S28) whose function is unclear. To assess the importance of H3S28, we generated a Drosophila H3 histone mutant with a serine-to-alanine mutation at position 28. H3S28A mutant cells lack H3S28ph on mitotic chromosomes but support normal mitosis. Strikingly, all methylation states of H3K27 drop in H3S28A cells, leading to Hox gene derepression and to homeotic transformations in adult tissues. These defects are not caused by active H3K27 demethylation nor by the loss of H3S28ph. Biochemical assays show that H3S28A nucleosomes are a suboptimal substrate for PRC2, suggesting that the unphosphorylated state of serine 28 is important for assisting in the function of polycomb complexes. Collectively, our data indicate that the conserved H3S28 residue in metazoans has a role in supporting PRC2 catalysis.
authors.affiliation: Institute of Human Genetics, UPR1142 CNRS, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors.forename: Philip Yuk Kwong
authors.initials: PY
authors.lastname: Yung
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stuetzer
authors.affiliation: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: wfischl@gwdg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Fischle
authors.affiliation: Institute of Human Genetics, UPR1142 CNRS, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France; Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France. Electronic address: anne-marie.martinez@igh.cnrs.fr.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Martinez
authors.affiliation: Institute of Human Genetics, UPR1142 CNRS, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France. Electronic address: giacomo.cavalli@igh.cnrs.fr.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cavalli
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019175:DNA Methylation; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006657:Histones / Q000235:genetics*; D007150:Immunohistochemistry; D063146:Polycomb-Group Proteins / Q000235:genetics* / Q000378:metabolism; D012694:Serine
chemical_list: D029721:Drosophila Proteins; D006657:Histones; D063146:Polycomb-Group Proteins; D012694:Serine; D011495:Histone-Lysine N-Methyltransferase; C524066:PRC2 protein, Drosophila