Whether non-DNA sequence information (i.e., epigenetic information) can be heritable and have a phenotypic effect at later generations is a long-standing question for biologists. The answer appears to be yes. A landmark population study showed that grandchildren of World War II Dutch Hunger famine survivors had lower-than-normal weight. The ability of transmitting epigenetic information through cell cycle and generational boundaries is an essential component of gene regulation and developmental control, yet the molecular mechanisms remain elusive.
The Gu lab primarily uses nematode C. elegans in our combined experimental and computational approaches. Our investigation focuses on two critical aspects of epigenetic regulation: (1) what triggers an epigenetic memory and (2) how epigenetic signals are transmitted through generational boundaries? We work on one mechanism that leads to a multigenerational epigenetic effect: RNA-induced chromatin modification. We found that the RNA-induced chromatin modification can last for multiple generations after the initial RNA exposure in C. elegans. A large number of human genes are now known to be physiological targets of RNA-directed chromatin modification. We would like to expand discoveries in C. elegans into human, with a focus on novel modes of RNA-chromatin interaction and epigenetic inheritance.