Repo-Man / PP 1 regulates heterochromatin formation 1 in interphase

General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. Abstract 30 31 Repo-Man is a Protein Phosphatase 1 (PP1) targeting subunit that regulates 32 mitotic progression and chromatin remodelling. After mitosis, Repo-Man/PP1 33 remains associated with chromatin but its function in interphase is not known. 34 Here we show that Repo-Man, via Nup153, is enriched on condensed 35 chromatin at the nuclear periphery and at the edge of the nucleopore basket. 36 Repo-Man/PP1 regulates the formation of heterochromatin, de-37 phosphorylates H3S28 and it is necessary and sufficient for HP1 binding and 38 H3K27me3 recruitment. Using a novel proteo-genomic approach, we show 39 that Repo-Man is enriched at sub-telomeric regions together with H2AZ and 40 H3.3 and that depletion of Repo-Man alters the peripheral localisation of a 41 subset of these regions and alleviates repression of some polycomb telomeric 42 genes. This study shows a role for a mitotic phosphatase in the regulation of 43 the epigenetic landscape and gene expression in interphase.