EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells

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 W. T. C. Jansen, Nicolas Servant, Maria-Elena Torres-Padilla, Deborah Bourc’his, Pierre Fouchet, Michiel Vermeulen and Raphaël Margueron ()
Additional contact information
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
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
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
Maria-Elena Torres-Padilla: Helmholtz Zentrum München
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

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11800-x

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