EZHIP Constrains Polycomb Repressive Complex 2 Activity in Germ Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Aug 28

PMID 31451685

Citations 53

Authors

Roberta Ragazzini

Raquel Perez-Palacios

Irem H Baymaz

Seynabou Diop

Katia Ancelin

Dina Zielinski

Audrey Michaud

Maelle Givelet

Mate Borsos

Setareh Aflaki

Patricia Legoix

Pascal W T C Jansen

Nicolas Servant

Maria-Elena Torres-Padilla

Deborah Bourchis

Pierre Fouchet

Michiel Vermeulen

Raphael Margueron

Affiliations

Soon will be listed here.

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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