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 relevant pathways.
We are focussed on investigating genes encoding for products that putatively interact with epigenetic signals involved in TEI, such as histone modifications and small RNAs. While searching for potential readers of H3K23 trimethylation, a histone modification implicated in TEI, two uncharacterised genes of interest were flagged: tag-250 and Y50D4C.3. To investigate their structures, we employed AlphaFold and compared putative domains to solved protein structures using the Dali server. Through this, we were able to identify the predicted location of these proteins’ Tudor domains, structures which commonly bind methylated protein residues. TAG-250 was additionally found to possess a LOTUS domain, a conserved structure only found in a handful of C. elegans proteins thus far and has been implicated in germ granule organisation. Furthermore, Y50D4C.3’s structural similarity with human protein TDRD3 was explored and their homologous domain architecture 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 ongoing plans to characterise these genes’ roles in epigenetic pathways and TEI.