title: H3K23me2 is a new heterochromatic mark in Caenorhabditis elegans.
abstract: Genome-wide analyses in Caenorhabditis elegans show that post-translational modifications (PTMs) of histones are evolutionary conserved and distributed along functionally distinct genomic domains. However, a global profile of PTMs and their co-occurrence on the same histone tail has not been described in this organism. We used mass spectrometry based middle-down proteomics to analyze histone H3 N-terminal tails from C. elegans embryos for the presence, the relative abundance and the potential cross-talk of co-existing PTMs. This analysis highlighted that the lysine 23 of histone H3 (H3K23) is extensively modified by methylation and that tri-methylated H3K9 (H3K9me3) is exclusively detected on histone tails with di-methylated H3K23 (H3K23me2). Chromatin immunoprecipitation approaches revealed a positive correlation between H3K23me2 and repressive marks. By immunofluorescence analyses, H3K23me2 appears differentially regulated in germ and somatic cells, in part by the action of the histone demethylase JMJD-1.2. H3K23me2 is enriched in heterochromatic regions, localizing in H3K9me3 and heterochromatin protein like-1 (HPL-1)-positive foci. Biochemical analyses indicated that HPL-1 binds to H3K23me2 and interacts with a conserved CoREST repressive complex. Thus, our study suggests that H3K23me2 defines repressive domains and contributes to organizing the genome in distinct heterochromatic regions during embryogenesis.
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Julien
authors.initials: J
authors.lastname: Vandamme
authors.affiliation: Centre for Epigenetics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, 5230 Odense M, Denmark.
authors.forename: Simone
authors.initials: S
authors.lastname: Sidoli
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Luca
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Friis
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Christensen
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark The Danish Stem Cell Centre (Danstem), University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
authors.affiliation: Centre for Epigenetics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, 5230 Odense M, Denmark.
authors.forename: Ole N
authors.initials: ON
authors.lastname: Jensen
authors.affiliation: Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark lisa.salcini@bric.ku.dk.
authors.forename: Anna Elisabetta
authors.initials: AE
authors.lastname: Salcini
mesh_terms: D000107:Acetylation; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis; D056970:Co-Repressor Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D005854:Germ Cells / Q000378:metabolism; D006570:Heterochromatin / Q000378:metabolism*; D042421:Histone Code; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D011499:Protein Processing, Post-Translational
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D056970:Co-Repressor Proteins; C525194:HPL-1 protein, C elegans; D006570:Heterochromatin; D006657:Histones; D056466:Histone Demethylases; D008239:Lysine