EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells

• DOI: 10.1038/s41467-019-11800-x
• Publication Date: 2019-08-26T10:02:41Z
• Authors: Roberta Ragazzini; Raquel Pérez-Pala...; Irem H. Baymaz; Seynabou Diop; Katia Ancelin; Dina Zielinski; Audrey Michaud; Maëlle Givelet; Mate Borsos; Setareh Aflaki; Patricia Legoix; Pascal W. T. C. J...; Nicolas Servant; Maria-Elena Torre...; Deborah Bourc’his; Pierre Fouchet; Michiel Vermeulen; Raphaël Margueron
• Keywords: Adult; Male; 0301 basic medicine; 570; Science; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry; Article; Histones; Mice; 03 medical and health sciences; Oogenesis; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]; Cell Line, Tumor; Sf9 Cells; Animals; Humans; Spermatogenesis; Ovum; Mice, Knockout; Oncogene Proteins; Molecular Biology/Genomics [q-bio.GN]; 0303 health sciences; Proteomics and Chromatin Biology; Q; Ovary; Polycomb Repressive Complex 2; Chromatin; Recombinant Proteins; HEK293 Cells; Mutation; Female

AbstractThe 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.