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, iphone 13 atlanta 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 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 hbl5266ca and (2) the rate-limiting step of 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.