Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance

PRC2 功能降低会改变男性生殖系表观遗传编程和父系遗传

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作者:Jessica M Stringer, Samuel C Forster, Zhipeng Qu, Lexie Prokopuk, Moira K O'Bryan, David K Gardner, Stefan J White, David Adelson, Patrick S Western

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.

Conclusion

This study reveals a novel role for the histone-modifying complex, PRC2, in paternal intergenerational transmission of epigenetic effects on offspring, with important implications for understanding disease inheritance.

Results

Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in foetal 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.

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