Transgenerational epigenetic inheritance in C.elegans. (360G-Wellcome-093970_Z_10_Z)

Transgenerational epigenetics is the study of changes in gene regulation, inheritable over generations that are not due to changes in the DNA sequence. Although a few examples of epialleles have been observed in nature, and are often associated with inheritable DNA methylation, the molecular mechanisms underlying this alternative type of heredity remain poorly understood. The soil nematode Caenorhabditis elegans exhibits a transgenerational memory of RNAi-instructed gene silencing although this organism does not exhibit DNA methylation. This project aims to determine the mode of transmission of epigenetic marks between generations. We hypothesize that small RNAs will play a role in this process. We will address this question in two ways: 1) We will study the mechanism of transgenerational epigenetic inheritance at a transgene locus, focussing on chromatin and small RNAs as likely candidates. 2) We will determine whether small RNA populations are sensitive to environment and whether this can affect offspring phenotype. A mechanism such as this would enable organisms to fine-tune expression of sensitive genes resulting in a fast, heritable, but reversible response to a changing environment.