Mounting evidence in a number of organisms suggests that some epigenetic modifications acquired by an individual during its lifetime can be inherited for multiple future generations. This phenomenon is termed transgenerational epigenetic inheritance, and may provide a mechanism for the inheritance of environmentally acquired traits. I am studying transgenerational epigenetic inheritance using a model organism, the nematode C. elegans.

We have developed a system in which RNAi-induced silencing of a GFP transgene is robustly inherited for multiple generations in the absence of the initial RNAi trigger. We show that the histone methyltransferase SET-25 and the putative histone methyltransferase SET-32 are required for effective transmission of transgene silencing. Both SET-25 and SET-32 are completely uncharacterised, and so we are investigating their functions. C. elegans populations are predominantly comprised of hermaphrodites which self-reproduce by internal self-fertilisation with a limited number of sperm. We show that set-32 mutant hermaphrodites have reduced fertility, producing fewer live offspring, fewer total eggs and more unfertilized eggs in comparison to wild type animals. This indicates decreased egg production and decreased self-sperm production and/or fertilisation, suggesting defects in both the male and female germline. Preliminary results also suggest that set-32 mutant animals display extended lifespan, consistent with the known inverse relationship between fertility and lifespan. Conversely, set-25 mutant animals display fertility and lifespan comparable to wild type.

Furthermore, using a GFP transcriptional reporter we demonstrate SET-32 expression in the intestine and in two neurons in the head. Preliminary data also suggests a potential role for SET-32 and SET-25 in foraging behaviour and/or chemosensation, which may be associated with the neuronal expression we identified, and data from these assays will be presented.