Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance.

Background: Defining the mechanisms that establish and regulate the transmission of epigenetic information from parent to offspring is critical for understanding disease heredity. Currently, the molecular pathways that regulate epigenetic information in the germline and its transmission to offspring are poorly understood. Results: Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance, both at the phenotypic and molecular levels. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in fetal male germ cells. Males with reduced PRC2 function produced offspring that over-expressed retrotransposed pseudogenes and had altered preimplantation embryo cleavage rates and cell cycle control. Conclusion: This study reveals a novel role for the histone modifying complex, PRC2, in epigenetic inheritance, with important implications for understanding disease inheritance. ChIPseq experiment using H3K27me3 specific antibody. Eight replicates of OCT4GFP FACS purified E15.5 fetal male germ cells from Eedwt/wt (n=4) and Eedhypo/hypo (n=4) mice were compared, using Eedwt/wt samples as control vs Eedhypo/hypo germ cells as test samples.