It has recently become clear that in some circumstances Lamarck may have been right. There are a growing number of examples where a clear case can be made for the inheritance from parent to offspring of environmentally acquired gene expression changes. The more complex and outbred the organism however, the more difficult this inheritance is to study. We study this phenomenon using a model organism, the nematode C. elegans.
We have developed a sensor in which RNAi-induced silencing of a GFP transgene is robustly inherited for multiple generations in the absence of the initial RNAi trigger. Using this sensor we have discovered a core set of nuclear RNAi and chromatin pathway genes that are necessary for effective transmission of epigenetic silencing between generations. These include an RNA-binding argonaute protein and putative histone methyltransferases, suggesting that both small RNAs and chromatin modifications are necessary for effective transmission of epigenetic silencing between generations.
Recently we have used the exquisite sensitivity of our sensor to demonstrate that the putative histone methyltransferases SET-25 and SET-32 are required for establishment of a transgenerational silencing signal but not for long-term maintenance of this signal between subsequent generations. This suggests that transgenerational epigenetic inheritance (TEI) is a multi-step process with distinct genetic requirements for establishment and maintenance of heritable silencing. We have recently expanded this work to determine the temporal requirement for another four proteins, doubling the known network of TEI genes. This work gives us mechanistic insight into the complicated process of transgenerational epigenetic inheritance.
Furthermore, small RNA sequencing reveals that the abundance of secondary siRNAs (thought to be the effector molecules of heritable silencing) does not correlate with silencing phenotypes. Together, our results suggest that the current mechanistic models of epigenetic inheritance are incomplete.