期刊
CELL REPORTS
卷 25, 期 8, 页码 2273-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.10.086
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资金
- Busch Biomedical Grant
- National Institute of General Medical Sciences of the NIH, United States [R01GM111752]
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM111752] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [P40OD010440] Funding Source: NIH RePORTER
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 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 the establishment phase is a transgenerational, chromatin-based process.
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