Repo-Man/PP1 regulates heterochromatin formation in interphase

Ines J de Castro, James Budzak, Maria L Giacinto, Lorena Ligammari, Ezgi Gokhan, Christos Spanos, Daniela Moralli, Christine Richardson, Jose de las Heras, Silvia Salatino, Eric Schirmer, Kathrine Ullman, Wendy Bickmore, Catherine Green, Juri Rappsilber, Sarah Lamble, Martin W Goldberg, Veronica Vinciotti, P. Vagnarelli

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article number14048
Number of pages15
JournalNature Communications
Early online date16 Jan 2017
Publication statusPublished - 2017


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