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)

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    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
    Volume25
    Issue number6
    DOIs
    Publication statusPublished - 15 Mar 2014

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    S 10
    Phosphotransferases
    Aurora Kinase B
    Genes
    RNA Polymerase II
    Methyltransferases
    Osteoblasts
    Mitogens
    Epigenomics
    Histones
    B-Lymphocytes
    Phosphorylation

    Cite this

    Sabbattini, P., Sjoberg, M., Nikic, S., Frangini, A., Holmqvist, P-H., Kunowska, N., ... 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
    Sabbattini, Pierangela ; Sjoberg, Marcela ; Nikic, Svetlana ; Frangini, Alberto ; Holmqvist, Per-Henrik ; Kunowska, Natalia ; Carroll, Tom ; Brookes, Emily ; Arthur, Simon J. ; Pombo, Ana ; Dillon, Niall. / A H3K9/S10 methyl-phospho switch modulates Polycomb and Pol II binding at repressed genes during differentiation. In: Molecular Biology of the Cell. 2014 ; Vol. 25, No. 6. pp. 904-915.
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    abstract = "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.",
    author = "Pierangela Sabbattini and Marcela Sjoberg and Svetlana Nikic and Alberto Frangini and Per-Henrik Holmqvist and Natalia Kunowska and Tom Carroll and Emily Brookes and Arthur, {Simon J.} and Ana Pombo and Niall Dillon",
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    Sabbattini, P, Sjoberg, M, Nikic, S, Frangini, A, Holmqvist, P-H, Kunowska, N, Carroll, T, Brookes, E, Arthur, SJ, 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, vol. 25, no. 6, pp. 904-915. https://doi.org/10.1091/mbc.E13-10-0628

    A H3K9/S10 methyl-phospho switch modulates Polycomb and Pol II binding at repressed genes during differentiation. / Sabbattini, Pierangela; Sjoberg, Marcela; Nikic, Svetlana; Frangini, Alberto; Holmqvist, Per-Henrik; Kunowska, Natalia; Carroll, Tom; Brookes, Emily; Arthur, Simon J.; Pombo, Ana; Dillon, Niall (Lead / Corresponding author).

    In: Molecular Biology of the Cell, Vol. 25, No. 6, 15.03.2014, p. 904-915.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A H3K9/S10 methyl-phospho switch modulates Polycomb and Pol II binding at repressed genes during differentiation

    AU - Sabbattini, Pierangela

    AU - Sjoberg, Marcela

    AU - Nikic, Svetlana

    AU - Frangini, Alberto

    AU - Holmqvist, Per-Henrik

    AU - Kunowska, Natalia

    AU - Carroll, Tom

    AU - Brookes, Emily

    AU - Arthur, Simon J.

    AU - Pombo, Ana

    AU - Dillon, Niall

    PY - 2014/3/15

    Y1 - 2014/3/15

    N2 - 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.

    AB - 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.

    U2 - 10.1091/mbc.E13-10-0628

    DO - 10.1091/mbc.E13-10-0628

    M3 - Article

    VL - 25

    SP - 904

    EP - 915

    JO - Molecular Biology of the Cell

    JF - Molecular Biology of the Cell

    SN - 1059-1524

    IS - 6

    ER -