Repo-Man/PP1 regulates heterochromatin formation in interphase

Inês J. de Castro, James Budzak, Maria L. Di Giacinto, Lorena Ligammari, Ezgi Gokhan, Christos Spanos, Daniela Moralli, Christine Richardson, Jose I. de las Heras, Silvia Salatino, Eric C. Schirmer, Katharine S. Ullman, Wendy A. Bickmore, Catherine Green, Juri Rappsilber, Sarah Lamble, Martin W. Goldberg, Veronica Vinciotti and Paola Vagnarelli ()
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Inês J. de Castro: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London
James Budzak: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London
Maria L. Di Giacinto: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London
Lorena Ligammari: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London
Ezgi Gokhan: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London
Christos Spanos: Wellcome Trust Centre for Cell Biology
Daniela Moralli: Wellcome Trust Centre for Human Genetics, University of Oxford
Christine Richardson: School of Biological and Medical Science, Durham University
Jose I. de las Heras: Wellcome Trust Centre for Cell Biology
Silvia Salatino: Wellcome Trust Centre for Human Genetics, University of Oxford
Eric C. Schirmer: Wellcome Trust Centre for Cell Biology
Katharine S. Ullman: Huntsman Cancer Institute, University of Utah
Wendy A. Bickmore: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh
Catherine Green: Wellcome Trust Centre for Human Genetics, University of Oxford
Juri Rappsilber: Wellcome Trust Centre for Cell Biology
Sarah Lamble: Wellcome Trust Centre for Human Genetics, University of Oxford
Martin W. Goldberg: School of Biological and Medical Science, Durham University
Veronica Vinciotti: College of Engineering, Design and Technology, Research Institute for Environment Health and Society, Brunel University London
Paola Vagnarelli: College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14048

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