Journal
CELL
Volume 182, Issue 5, Pages 1186-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.07.022
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Funding
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- Adelis Foundation [0604916191]
- ERC [335624, 819151]
- European Research Council (ERC) [335624, 819151] Funding Source: European Research Council (ERC)
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Experiences trigger transgenerational small RNA-based responses in C. elegans nematodes. Dedicated machinery ensures that heritable effects are reset, but how the responses segregate in the population is unknown. We show that isogenic individuals differ dramatically in the persistence of transgenerational responses. By examining lineages of more than 20,000 worms, three principles emerge: (1) The silencing each mother initiates is distributed evenly among her descendants; heritable RNAi dissipates but is uniform in every generation. (2) Differences between lineages arise because the mothers that initiate heritable responses stochastically assume different inheritance states'' that determine the progeny's fate. (3) The likelihood that an RNAi response would continue to be inherited increases the more generations it lasts. The inheritance states are determined by HSF-1, which regulates silencing factors and, accordingly, small RNA levels. We found that, based on the parents' inheritance state, the descendants' developmental rate in response to stress can be predicted.
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