While it has traditionally been thought that acquired traits cannot be inherited from parent to offspring, growing evidence suggests that signals from an organism’s environment can result in the transmission of non-genetic information. We use Caenorhabditis elegans to study this phenomenon, termed transgenerational epigenetic inheritance (TEI). Using this model to examine the transmission of environmentally induced epigenetic gene silencing to subsequent generations, several genes required for this process have been identified. However, many aspects of TEI remain mysterious, and our goal is to identify and characterise novel members of the pathway.
Given there is an established link between TEI and epigenetic signals such as histone modifications and small RNAs, we are focussed on investigating genes encoding for proteins that putatively interact with such molecules. Whilst searching for readers of a H3K23me3, a histone mark implicated in TEI, two uncharacterised genes of interest were flagged: tag-250 and Y50D4C.3. We employed AlphaFold to investigate their structures and used the Dali server to compare putative domains to solved protein structures. The predicted location of these proteins’ Tudor domains, which commonly bind methylated protein residues, was identified. TAG-250 was also found to possess a LOTUS domain, a conserved RNA-binding domain implicated in germ granule organisation, which in C. elegans has only been found in a handful of proteins thus far. Furthermore, Y50D4C.3’s structural similarity with human protein TDRD3 was explored and the location of homologous domains confirmed. The identification of previously unannotated domains presents new avenues of investigation, and we will present on these results to date as well as our plans to characterise these genes’ roles in epigenetic pathways and TEI.