2. Academic Validation
  3. EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells

EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells

  • Nat Commun. 2019 Aug 26;10(1):3858. doi: 10.1038/s41467-019-11800-x.
Roberta Ragazzini 1,  Raquel Pérez-Palacios 1,  Irem H Baymaz 2,  Seynabou Diop 1,  Katia Ancelin 1,  Dina Zielinski 1 3,  Audrey Michaud 1,  Maëlle Givelet 4,  Mate Borsos 5 6,  Setareh Aflaki 1,  Patricia Legoix 7,  Pascal W T C Jansen 2,  Nicolas Servant 1 3,  Maria-Elena Torres-Padilla 5 6,  Deborah Bourc'his 1,  Pierre Fouchet 4,  Michiel Vermeulen 2,  Raphaël Margueron 8
Affiliations

Affiliations

  • 1 Institut Curie, PSL Research University, Sorbonne University, INSERM U934/ CNRS UMR3215, 26, rue d'Ulm, 75005, Paris, France.
  • 2 Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Route 274 M850.03.87 Geert Grooteplein 28, Nijmegen, 6525, GA, Netherlands.
  • 3 INSERM U900, Mines ParisTech, 26, rue d'Ulm, Paris, France.
  • 4 Commissariat à l'énergie atomique et aux énergies alternatives, Institut de radiobiologie cellulaire et moléculaire, Laboratoire des Cellules Souches Germinales, INSERM U967, Fontenay-aux-Roses, 92260, France.
  • 5 Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, D-81377, München, Germany.
  • 6 Faculty of Biology, Ludwig Maximilians Universität, D-81377, München, Germany.
  • 7 ICGex Next-Generation Sequencing Platform, Curie Institute, 26, rue d'Ulm, Paris, France.
  • 8 Institut Curie, PSL Research University, Sorbonne University, INSERM U934/ CNRS UMR3215, 26, rue d'Ulm, 75005, Paris, France. [email protected].
PMID: 31451685 DOI: 10.1038/s41467-019-11800-x
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.

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