Transgenerational_epigenetic_inheritance__embryos. Transgenerational_epigenetic_inheritance__embryos

Transgenerational epigenetic effects likely have wide-ranging implications for human health, biological adaptation and evolution, however their mechanisms remain poorly understood. We recently demonstrated that a germline nuclear RNA and chromatin pathway maintains gene silencing stably for many generations in the nematode Caenorhabditis elegans. We hypothesise that transgenerational epigenetic inheritance (TEI) is the consequence of interactions between repetitive and genic parts of the genome mediated by small RNA. We will investigate the mechanisms underlying TEI, determine if and how TEI provides an environmental memory (“Lamarckism”) and examine its implications for genome stability and evolution. Our questions are: (1) What are the mechanisms underlying transgenerational epigenetic inheritance? (2) How does the environment shape the transgenerational epigenetic landscape to anticipate the phenotype of the next generation? (3) How do transgenerational epigenetic effects shape the distributions of the genetic and epigenetic landscape of populations? We will use the powerful molecular genetic tools available for the mouse. In addition, we will take advantage of recent advances in induced pluripotent stem cell (iPS) technology to translate our work to human. Briefly, we will use mouse tissue samples (JAX) and differentiated human iPS cells (in house) for small RNA sequencing, bisulfite sequencing and genome re-sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/