title: Repo-Man/PP1 regulates heterochromatin formation in interphase.
abstract: Repo-Man is a protein phosphatase 1 (PP1) targeting subunit that regulates mitotic progression and chromatin remodelling. After mitosis, Repo-Man/PP1 remains associated with chromatin but its function in interphase is not known. Here we show that Repo-Man, via Nup153, is enriched on condensed chromatin at the nuclear periphery and at the edge of the nucleopore basket. Repo-Man/PP1 regulates the formation of heterochromatin, dephosphorylates H3S28 and it is necessary and sufficient for heterochromatin protein 1 binding and H3K27me3 recruitment. Using a novel proteogenomic approach, we show that Repo-Man is enriched at subtelomeric regions together with H2AZ and H3.3 and that depletion of Repo-Man alters the peripheral localization of a subset of these regions and alleviates repression of some polycomb telomeric genes. This study shows a role for a mitotic phosphatase in the regulation of the epigenetic landscape and gene expression in interphase.
authors.affiliation: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
authors.forename: Inês J
authors.initials: IJ
authors.lastname: de Castro
authors.affiliation: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
authors.forename: James
authors.initials: J
authors.lastname: Budzak
authors.affiliation: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Di Giacinto
authors.affiliation: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
authors.forename: Lorena
authors.initials: L
authors.lastname: Ligammari
authors.affiliation: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Gokhan
authors.affiliation: Wellcome Trust Centre for Cell Biology, Edinburgh EH9 3BF, UK.
authors.forename: Christos
authors.initials: C
authors.lastname: Spanos
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Daniela
authors.initials: D
authors.lastname: Moralli
authors.affiliation: School of Biological and Medical Science, Durham University, Durham DH1 3LE, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Richardson
authors.affiliation: Wellcome Trust Centre for Cell Biology, Edinburgh EH9 3BF, UK.
authors.forename: Jose I
authors.initials: JI
authors.lastname: de Las Heras
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Salatino
authors.affiliation: Wellcome Trust Centre for Cell Biology, Edinburgh EH9 3BF, UK.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Schirmer
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Katharine S
authors.initials: KS
authors.lastname: Ullman
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Green
authors.affiliation: Wellcome Trust Centre for Cell Biology, Edinburgh EH9 3BF, UK.|Technische Universitat Berlin, 13355 Berlin, Germany.
authors.forename: Juri
authors.identifier: 0000-0001-5999-1310
authors.initials: J
authors.lastname: Rappsilber
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lamble
authors.affiliation: School of Biological and Medical Science, Durham University, Durham DH1 3LE, UK.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Goldberg
authors.affiliation: College of Engineering, Design and Technology, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
authors.forename: Veronica
authors.initials: V
authors.lastname: Vinciotti
authors.affiliation: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
authors.forename: Paola
authors.identifier: 0000-0002-0000-2271
authors.initials: P
authors.lastname: Vagnarelli
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007399:Interphase; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: C509224:CDCA2 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins