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Publication : EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells.

First Author  Ragazzini R Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  3858
PubMed ID  31451685 Mgi Jnum  J:281161
Mgi Id  MGI:6362099 Doi  10.1038/s41467-019-11800-x
Citation  Ragazzini R, et al. (2019) EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells. Nat Commun 10(1):3858
abstractText  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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