Affiliation:
1. Gene Center, Ludwig-Maximilians-Universität München , Munich, Germany
2. Department of Structural Biology, St. Jude Children's Research Hospital , 263 Danny Thomas Place, Memphis , TN 38105, USA
Abstract
Abstract
Heterochromatic silencing is thought to occur through a combination of transcriptional silencing and RNA degradation, but the relative contribution of each pathway is not known. In this study, we analyzed RNA Polymerase II (RNA Pol II) occupancy and levels of nascent and steady-state RNA in different mutants of Schizosaccharomyces pombe, in order to quantify the contribution of each pathway to heterochromatic silencing. We found that transcriptional silencing consists of two components, reduced RNA Pol II accessibility and, unexpectedly, reduced transcriptional efficiency. Heterochromatic loci showed lower transcriptional output compared to euchromatic loci, even when comparable amounts of RNA Pol II were present in both types of regions. We determined that the Ccr4–Not complex and H3K9 methylation are required for reduced transcriptional efficiency in heterochromatin and that a subset of heterochromatic RNA is degraded more rapidly than euchromatic RNA. Finally, we quantified the contribution of different chromatin modifiers, RNAi and RNA degradation to each silencing pathway. Our data show that several pathways contribute to heterochromatic silencing in a locus-specific manner and reveal transcriptional efficiency as a new mechanism of silencing.
Funder
St. Jude Children's Research Hospital
American Lebanese Syrian Associated Charities
ERC
NIH
Deutsche Forschungsgemeinschaft
Publisher
Oxford University Press (OUP)
Cited by
3 articles.
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