A H3K9/S10 methyl-phospho switch modulates Polycomb and Pol II binding at repressed genes during differentiation

Pierangela Sabbattini, Marcela Sjoberg, Svetlana Nikic, Alberto Frangini, Per-Henrik Holmqvist, Natalia Kunowska, Tom Carroll, Emily Brookes, Simon J. Arthur, Ana Pombo, Niall Dillon (Lead / Corresponding author)

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    Methylated histone H3K9 and H3K27 are canonical epigenetic silencing modifications in metazoan organisms, but the relationship between the two modifications has not been well characterised. We show that H3K9me3 coexists with H3K27me3 in pluripotent and differentiated cells. However, we find that the functioning of H3K9me3 is altered by H3S10 phosphorylation in differentiated postmitotic osteoblasts and in cycling B cells. Deposition of H3K9me3/S10ph at silent genes is partially mediated by the mitogen and stress activated kinases (MSK1/2) and the Aurora B kinase. Acquisition of H3K9me3/S10ph during differentiation correlates with loss of paused S5 phosphorylated RNA polymerase II, which is present on Polycomb-regulated genes in ES cells. Reduction of the levels of H3K9me3/S10ph by kinase inhibition results in increased binding of RNAPIIS5ph and of the H3K27 methyltransferase Ezh1 at silent promoters. Our results provide evidence of a novel developmentally regulated methyl-phospho switch that modulates Polycomb regulation in differentiated cells and stabilises repressed states.
    Original languageEnglish
    Pages (from-to)904-915
    Number of pages12
    JournalMolecular Biology of the Cell
    Issue number6
    Publication statusPublished - 15 Mar 2014


    Cite this

    Sabbattini, P., Sjoberg, M., Nikic, S., Frangini, A., Holmqvist, P-H., Kunowska, N., Carroll, T., Brookes, E., Arthur, S. J., Pombo, A., & Dillon, N. (2014). A H3K9/S10 methyl-phospho switch modulates Polycomb and Pol II binding at repressed genes during differentiation. Molecular Biology of the Cell, 25(6), 904-915. https://doi.org/10.1091/mbc.E13-10-0628