Scott Kennedy (University of Wisconsin)
MolBio Seminar Series
Multigenerational Epigenetic Inheritance and Germline Immortality
For most of the last century it was widely believed that (unlike genetic information) epigenetic information did not pass across generational boundaries. It is now known that this is not always the case. We are exploring how epigenetic information is inherited. dsRNA-mediate gene silencing (RNAi) can be heritable for many generations in the model organism C. elegans. We have conducted a genetic screen to identify cellular factors required for RNAi-mediated multigenerational epigenetic inheritance. This screen has shown that RNAi inheritance is mediated by cellular pathways that couples small interfering RNAs (siRNAs) to co-transcriptional gene silencing in nuclei (termed nuclear RNAi). Interestingly, we have found that during the normal course of reproduction, endogenously expressed small RNAs direct heritable gene silencing at specific genomic loci in C. elegans germ cells. In the absence of this gene regulatory system, germ cells lose their immortal character. These data have led us to propose that animals use the nuclear RNAi and RNAi inheritance machinery to transmit epigenetic information, accrued by past generations, into future generations to regulate important biological processes.
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