Diet Modulates Heritability of Epigenetic Silencing in Caenorhabditis elegans

Abstract

The dsRNA-transport protein sid-1 is silenced in the germline of animals that contain a multicopy array of the sid-1 promoter. Silencing of sid-1 is inherited in animals that have lost the array and is maintained in almost all subsequent offspring for up to 15 generations. I have found that the diet of array-carrying worms can dramatically affect the heritability of sid-1 silencing. While sid-1 silencing persists for many generations after array loss in animals fed the standard lab diet, the E. coli strain OP50, animals fed different E. coli strains, HB101 or HT115, fail to transmit silencing to their progeny that have lost the array. Diet and growth temperature does not affect sid-1 silencing in the presence of the array, only the inheritance of silencing after array loss. The severity of diet on inherited silencing is modulated by worm growth temperature. The effect of altered diets and growth temperature accumulates over multiple generations and can be reversed by returning to the past environment. Furthermore, this effect is also observed when animals are fed different bacteria associated with the C. elegans natural microbiome; monocultures of some microbiome foods extend silencing for multiple generations, and some eliminate heritable silencing, thus providing an ecological context and evolutionary implications for this discovery. The number of sid-1 antisense small RNAs is decreased in array-carrying worms grown in conditions that fail to transmit silencing, thus directly linking small RNA abundance to the expected environmental conditions. It is surprising that altered diet and growth temperature have such a profound effect on an otherwise stable and persistent signal. My work is an example of the integration of environmental signals and genomic surveillance that modulate the heritability of epigenetic states.