Repo-Man/PP1 regulates heterochromatin formation in interphase.
de Castro IJ., Budzak J., Di Giacinto ML., Ligammari L., Gokhan E., Spanos C., Moralli D., Richardson C., de Las Heras JI., Salatino S., Schirmer EC., Ullman KS., Bickmore WA., Green C., Rappsilber J., Lamble S., Goldberg MW., Vinciotti V., Vagnarelli P.
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.