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EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells

Author

Listed:
  • Roberta Ragazzini

    (Sorbonne University, INSERM U934/ CNRS UMR3215)

  • Raquel Pérez-Palacios

    (Sorbonne University, INSERM U934/ CNRS UMR3215)

  • Irem H. Baymaz

    (Radboud University Nijmegen)

  • Seynabou Diop

    (Sorbonne University, INSERM U934/ CNRS UMR3215)

  • Katia Ancelin

    (Sorbonne University, INSERM U934/ CNRS UMR3215)

  • Dina Zielinski

    (Sorbonne University, INSERM U934/ CNRS UMR3215
    INSERM U900, Mines ParisTech)

  • Audrey Michaud

    (Sorbonne University, INSERM U934/ CNRS UMR3215)

  • Maëlle Givelet

    (Commissariat à l’énergie atomique et aux énergies alternatives, Institut de radiobiologie cellulaire et moléculaire, Laboratoire des Cellules Souches Germinales, INSERM U967)

  • Mate Borsos

    (Helmholtz Zentrum München
    Ludwig Maximilians Universität)

  • Setareh Aflaki

    (Sorbonne University, INSERM U934/ CNRS UMR3215)

  • Patricia Legoix

    (ICGex Next-Generation Sequencing Platform, Curie Institute)

  • Pascal W. T. C. Jansen

    (Radboud University Nijmegen)

  • Nicolas Servant

    (Sorbonne University, INSERM U934/ CNRS UMR3215
    INSERM U900, Mines ParisTech)

  • Maria-Elena Torres-Padilla

    (Helmholtz Zentrum München
    Ludwig Maximilians Universität)

  • Deborah Bourc’his

    (Sorbonne University, INSERM U934/ CNRS UMR3215)

  • Pierre Fouchet

    (Commissariat à l’énergie atomique et aux énergies alternatives, Institut de radiobiologie cellulaire et moléculaire, Laboratoire des Cellules Souches Germinales, INSERM U967)

  • Michiel Vermeulen

    (Radboud University Nijmegen)

  • Raphaël Margueron

    (Sorbonne University, INSERM U934/ CNRS UMR3215)

Abstract

The Polycomb group of proteins is required for the proper orchestration of gene expression due to its role in maintaining transcriptional silencing. It is composed of several chromatin modifying complexes, including Polycomb Repressive Complex 2 (PRC2), which deposits H3K27me2/3. Here, we report the identification of a cofactor of PRC2, EZHIP (EZH1/2 Inhibitory Protein), expressed predominantly in the gonads. EZHIP limits the enzymatic activity of PRC2 and lessens the interaction between the core complex and its accessory subunits, but does not interfere with PRC2 recruitment to chromatin. Deletion of Ezhip in mice leads to a global increase in H3K27me2/3 deposition both during spermatogenesis and at late stages of oocyte maturation. This does not affect the initial number of follicles but is associated with a reduction of follicles in aging. Our results suggest that mature oocytes Ezhip−/− might not be fully functional and indicate that fertility is strongly impaired in Ezhip−/− females. Altogether, our study uncovers EZHIP as a regulator of chromatin landscape in gametes.

Suggested Citation

  • Roberta Ragazzini & Raquel Pérez-Palacios & Irem H. Baymaz & Seynabou Diop & Katia Ancelin & Dina Zielinski & Audrey Michaud & Maëlle Givelet & Mate Borsos & Setareh Aflaki & Patricia Legoix & Pascal , 2019. "EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11800-x
    DOI: 10.1038/s41467-019-11800-x
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    Cited by:

    1. Lihu Gong & Xiuli Liu & Lianying Jiao & Xin Yang & Andrew Lemoff & Xin Liu, 2022. "CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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