C. elegans Heterochromatin Factor SET-32 Plays an Essential Role in Transgenerational Establishment of Nuclear RNAi-Mediated Epigenetic Silencing

C. elegans Heterochromatin Factor SET-32 Plays an Essential Role in Transgenerational Establishment of Nuclear RNAi-Mediated Epigenetic Silencing

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Summary: The dynamic process by which nuclear RNAi engages a transcriptionally active target, before the repressive state is stably established, remains largely a mystery.Here, we found that the onset of exogenous dsRNA-induced nuclear RNAi in C.elegans is a transgenerational process, and it requires a putative histone methyltransferase (HMT), SET-32.

By developing a CRISPR-based genetic approach, we found that silencing establishment at the endogenous targets of germline nuclear RNAi also requires SET-32.Although SET-32 and two H3K9 HMTs, MET-2 and SET-25, are dispensable for the maintenance of silencing, they do contribute to transcriptional Neff D65IBE1S0B 60cm Wide Angled Cooker Hood With Perimeter Extractio repression in mutants that lack the germline nuclear Argonaute protein HRDE-1, suggesting a conditional role of heterochromatin in the maintenance phase.Our study indicates that (1) establishment and maintenance of siRNA-guided transcriptional repression are two distinct processes with different genetic requirements and (2) the rate-limiting step of Outdoor Accessory the establishment phase is a transgenerational, chromatin-based process.

: Deciphering mechanisms of transgenerational epigenetic gene regulation is critical for understanding of development, aging, and disease.In this study, Kalinava et al.examine the establishment of RNAi-mediated epigenetic silencing.

The identification of the bottleneck step provides critical insight into the regulation of this pathway.Keywords: nuclear RNAi, epigenetic silencing, transgenerational epigenetic inheritance, heterochromatin, silencing establishment, CRISPR, MET-2, SET-25, SET-32, HRDE-1.