Epigetic programming in the germline : establishing a foundation for the next generation

Fetal germ cells are the precursors of oocytes (eggs) and sperm, which transmit an individual’s genetic and epigenetic information to the offspring. Significantly, errors in germline epigenetic programming can alter the epigenome and change offspring development and health. Epigenetic modifications primarily involve DNA methylation and covalent modifications of the histone proteins that facilitate organised packaging of the chromatin into the nucleus.  During germ cell development, DNA methylation is initially removed and new DNA methylation is established, providing sex-specific epigenomes in sperm and eggs that are required for development in the next generation. However, the role of histone modifications in germline epigenetic programming is poorly understood. Using models in which the essential epigenetic modifying complex PRC2 is disrupted in during male and female germline development, we have identified roles for the histone modification, H3K27me3, in germline reprogramming and epigenetic inheritance. Our findings indicate that PRC2 and H3K27me3 provide a novel, functionally important mechanism that modulates inheritance through the male and female germlines. Understanding these mechanisms will provide important insight into the contributions of epigenetic modifications to inherited disease and the impacts of environmental factors, such as drugs and diet that may alter the germline epigenome and change outcomes in our offspring.