ABSTRACT
The Polycomb machinery is required for the proper orchestration of gene expression by virtue of its critical 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 new cofactor of PRC2, GPIF (Gonads PRC2 Inhibitory Factor), expressed predominantly in the gonad. GPIF limits the enzymatic activity of PRC2 by lessening the interaction between the core complex and its accessory subunits, but without interfering with its recruitment to chromatin. Deletion of Gpif leads to a global increase of H3K27me2/3 deposition both during spermatogenesis and at late stages of oocyte maturation. This alteration of the epigenetic content of mature oocytes does not affect the initial pool of follicles but is associated with a reduction in follicle number in aging mice. In addition, fertility is strongly impaired in Gpif −/− females indicative of developmental defects emerging around fertilization or during embryo development. Our study uncovers GPIF as a novel functional player in the comprehensive chromatin remodeling that occurs in the gonad.