The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Epigenetic Regulation in the Germline: Setting a Foundation for the Next Generation. (#167)

Patrick Western 1
  1. Hudson Institute for Medical Research, CLAYTON, VIC, Australia

The development of a complex multicellular organism involves the production of a remarkable array of specialised cells from a single genomic sequence. This is facilitated by heritable epigenetic modifications that organise the DNA into active and repressed domains, allowing the regulation of specific gene expression programs that direct cell specialisation. The transmission of epigenetic signatures between cell generations ensures the maintenance of lineage specific expression profiles, and appropriate cell and tissue function throughout life. Cell type specific epigenomic information is not only important in somatic cell specialisation, but also regulates germline differentiation and the transmission of information that affects the development and physiology of offspring. This is of particular interest as it is proposed that the epigenome provides an interface between the environment and genome function. However, the mechanisms involved in epigenetic patterning of the germline and the epigenetic modifications that affect offspring development are poorly understood. While many studies have focussed on the impacts of various environmental challenges on epigenetic inheritance, our studies have concentrated on the role of Polycomb Repressive Complex 2 (PRC2) in the germline. PRC2 is a highly conserved epigenetic modifier essential for establishing the repressive histone modification H3K27me3 and regulating development through repression of target genes. Using genetic and pharmacological approaches, our work provides evidence that PRC2 regulates H3K27me3 in developing germ cells and alters epigenetic inheritance through the maternal and paternal germlines. Of particular interest in this context are systemic epigenomic drugs that directly target epigenetic modifying proteins in target tissues such as tumours. While these drugs offer improved therapeutic approaches, they also have the potential to alter the germline epigenome. Given growing evidence that epigenetic inheritance is affected by environmental influences such as diet, chemicals and drugs, further understanding of mechanisms regulating the germline epigenome is required to gauge potential for environmental impacts on the germline to alter disease inheritance and evolution.