College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.
Wellcome Trust Centre for Cell Biology, Edinburgh EH9 3BF, UK.
Nat Commun. 2017 Jan 16;8:14048. doi: 10.1038/ncomms14048.
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.
Repo-Man 是一种蛋白磷酸酶 1（PP1）的靶向亚基，它调节有丝分裂的进程和染色质重塑。有丝分裂后，Repo-Man/PP1 仍然与染色质相关联，但它在间期中的功能尚不清楚。在这里，我们表明 Repo-Man 通过 Nup153 富集在核周的浓缩染色质和核孔篮的边缘。Repo-Man/PP1 调节异染色质的形成，去磷酸化 H3S28，并且对于异染色质蛋白 1 结合和 H3K27me3 的募集是必需和充分的。使用一种新的蛋白质基因组学方法，我们表明 Repo-Man 与 H2AZ 和 H3.3 一起富集在端粒区，并且 Repo-Man 的耗竭改变了这些区域的一部分外周定位，并缓解了一些多梳端粒基因的抑制。这项研究表明有丝分裂磷酸酶在调节间期的表观遗传景观和基因表达方面的作用。
