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Nat Commun. 2017 Jan 16;8:14048. doi: 10.1038/ncomms14048.

Repo-Man/PP1 regulates heterochromatin formation in interphase.

Author information

1
College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
2
Wellcome Trust Centre for Cell Biology, Edinburgh EH9 3BF, UK.
3
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
4
School of Biological and Medical Science, Durham University, Durham DH1 3LE, UK.
5
Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.
6
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
7
Technische Universitat Berlin, 13355 Berlin, Germany.
8
College of Engineering, Design and Technology, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.

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.

PMID:
28091603
PMCID:
PMC5241828
DOI:
10.1038/ncomms14048
[Indexed for MEDLINE]
Free PMC Article

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