A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin

Sarah Elderkin, Goedele N Maertens, Mitsuhiro Endoh, Donna L Mallery, Nick Morrice, Haruhiko Koseki, Gordon Peters, Neil Brockdorff, Kevin Hiom

    Research output: Contribution to journalArticle

    93 Citations (Scopus)

    Abstract

    Recent studies have shown that PRC1-like Polycomb repressor complexes monoubiquity-late chromatin on histone H2A at lysine residue 119. Here we have analyzed the function of the polycomb protein Mel-18. Using affinity-tagged human MEL-18, we identify a polycomb-like complex, melPRC1, containing the core PRC1 proteins, RING1/2, HPH2, and CBX8. We show that, in ES cells, melPRC1 can functionally substitute for other PRC1-like complexes in Hox gene repression. A reconstituted subcomplex containing only Ring1B and Mel-18 functions as an efficient ubiquitin E3 ligase. This complex ubiquitylates free histone substrates nonspecifically but is highly specific for histone H2A lysine 119 in the context of nucleosomes. Mutational analysis demonstrates that while Ring1B is required for E3 function, Mel-18 directs this activity to H2A lysine 119 in chromatin. Moreover, this substrate-targeting function of Mel-18 is dependent on its prior phosphorylation at multiple residues, providing a direct link between chromatin modification and cell signaling pathways.
    Original languageEnglish
    Pages (from-to)107-20
    Number of pages14
    JournalMolecular Cell
    Volume28
    Issue number1
    DOIs
    Publication statusPublished - 2007

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    Ligases
    Ubiquitin
    Histones
    Lysine
    Chromatin
    Polycomb-Group Proteins
    Ubiquitin-Protein Ligases
    Nucleosomes
    Homeobox Genes
    Proteins
    Phosphorylation

    Cite this

    Elderkin, Sarah ; Maertens, Goedele N ; Endoh, Mitsuhiro ; Mallery, Donna L ; Morrice, Nick ; Koseki, Haruhiko ; Peters, Gordon ; Brockdorff, Neil ; Hiom, Kevin. / A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin. In: Molecular Cell. 2007 ; Vol. 28, No. 1. pp. 107-20.
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    title = "A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin",
    abstract = "Recent studies have shown that PRC1-like Polycomb repressor complexes monoubiquity-late chromatin on histone H2A at lysine residue 119. Here we have analyzed the function of the polycomb protein Mel-18. Using affinity-tagged human MEL-18, we identify a polycomb-like complex, melPRC1, containing the core PRC1 proteins, RING1/2, HPH2, and CBX8. We show that, in ES cells, melPRC1 can functionally substitute for other PRC1-like complexes in Hox gene repression. A reconstituted subcomplex containing only Ring1B and Mel-18 functions as an efficient ubiquitin E3 ligase. This complex ubiquitylates free histone substrates nonspecifically but is highly specific for histone H2A lysine 119 in the context of nucleosomes. Mutational analysis demonstrates that while Ring1B is required for E3 function, Mel-18 directs this activity to H2A lysine 119 in chromatin. Moreover, this substrate-targeting function of Mel-18 is dependent on its prior phosphorylation at multiple residues, providing a direct link between chromatin modification and cell signaling pathways.",
    author = "Sarah Elderkin and Maertens, {Goedele N} and Mitsuhiro Endoh and Mallery, {Donna L} and Nick Morrice and Haruhiko Koseki and Gordon Peters and Neil Brockdorff and Kevin Hiom",
    year = "2007",
    doi = "10.1016/j.molcel.2007.08.009",
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    Elderkin, S, Maertens, GN, Endoh, M, Mallery, DL, Morrice, N, Koseki, H, Peters, G, Brockdorff, N & Hiom, K 2007, 'A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin', Molecular Cell, vol. 28, no. 1, pp. 107-20. https://doi.org/10.1016/j.molcel.2007.08.009

    A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin. / Elderkin, Sarah; Maertens, Goedele N; Endoh, Mitsuhiro; Mallery, Donna L; Morrice, Nick; Koseki, Haruhiko; Peters, Gordon; Brockdorff, Neil; Hiom, Kevin.

    In: Molecular Cell, Vol. 28, No. 1, 2007, p. 107-20.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin

    AU - Elderkin, Sarah

    AU - Maertens, Goedele N

    AU - Endoh, Mitsuhiro

    AU - Mallery, Donna L

    AU - Morrice, Nick

    AU - Koseki, Haruhiko

    AU - Peters, Gordon

    AU - Brockdorff, Neil

    AU - Hiom, Kevin

    PY - 2007

    Y1 - 2007

    N2 - Recent studies have shown that PRC1-like Polycomb repressor complexes monoubiquity-late chromatin on histone H2A at lysine residue 119. Here we have analyzed the function of the polycomb protein Mel-18. Using affinity-tagged human MEL-18, we identify a polycomb-like complex, melPRC1, containing the core PRC1 proteins, RING1/2, HPH2, and CBX8. We show that, in ES cells, melPRC1 can functionally substitute for other PRC1-like complexes in Hox gene repression. A reconstituted subcomplex containing only Ring1B and Mel-18 functions as an efficient ubiquitin E3 ligase. This complex ubiquitylates free histone substrates nonspecifically but is highly specific for histone H2A lysine 119 in the context of nucleosomes. Mutational analysis demonstrates that while Ring1B is required for E3 function, Mel-18 directs this activity to H2A lysine 119 in chromatin. Moreover, this substrate-targeting function of Mel-18 is dependent on its prior phosphorylation at multiple residues, providing a direct link between chromatin modification and cell signaling pathways.

    AB - Recent studies have shown that PRC1-like Polycomb repressor complexes monoubiquity-late chromatin on histone H2A at lysine residue 119. Here we have analyzed the function of the polycomb protein Mel-18. Using affinity-tagged human MEL-18, we identify a polycomb-like complex, melPRC1, containing the core PRC1 proteins, RING1/2, HPH2, and CBX8. We show that, in ES cells, melPRC1 can functionally substitute for other PRC1-like complexes in Hox gene repression. A reconstituted subcomplex containing only Ring1B and Mel-18 functions as an efficient ubiquitin E3 ligase. This complex ubiquitylates free histone substrates nonspecifically but is highly specific for histone H2A lysine 119 in the context of nucleosomes. Mutational analysis demonstrates that while Ring1B is required for E3 function, Mel-18 directs this activity to H2A lysine 119 in chromatin. Moreover, this substrate-targeting function of Mel-18 is dependent on its prior phosphorylation at multiple residues, providing a direct link between chromatin modification and cell signaling pathways.

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