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- W2405804937 abstract "Promoter-proximal pausing of RNA Pol II (Pol II) is a near universal feature of human genes and plays a central role in governing levels of transcription and modulating rapid response to stimuli. Here we show that at CpG island (CGI)- associated promoters, Pol II encounters an additional barrier to elongation distinct from the promoter-proximal pause that occurs at the downstream boundary of the CGI domain. For most CGI associated promoters, Pol II exhibits a dominant pause at either the promoter-proximal or this distal site that correlates, both in position and in intensity, with local regions of high GC skew, a sequence feature known to promote the formation of unique secondary structures. Indeed, we find that distally paused genes manifest longer or more stable R-loops, a structure suggested to protect CGI domains from DNA methylation. Interestingly, the link between GC-skew and Pol II pausing is conserved in Drosophila. Upon signal-induced gene activation, long-range enhancer contacts at the dominant pause site are selectively enhanced, suggesting a new role for enhancers at CGI boundaries. Consistent with this idea, we find a correlation between enrichment of the cohesin complex, important for DNA looping, and the position of the dominant pause site. These findings unearth a novel transcriptional regulatory step at CGI-associated genes that is dictated by the underlying DNA sequenceand linked to the integrity of the CGI domain. Citation Format: Joshua SK Bell, Wendy A. Kellner, Paula M. Vertino. GC skew defines distinct RNA polymerase pause sites in CpG island promoters. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr PR08." @default.
- W2405804937 created "2016-06-24" @default.
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- W2405804937 date "2016-01-14" @default.
- W2405804937 modified "2023-10-16" @default.
- W2405804937 title "Abstract PR08: GC skew defines distinct RNA polymerase pause sites in CpG island promoters" @default.
- W2405804937 doi "https://doi.org/10.1158/1538-7445.chromepi15-pr08" @default.
- W2405804937 hasPublicationYear "2016" @default.
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