RNA polymerase stalling potentiates gene activity by maintaining open chromatin structure
NIEHS researchers in the Transcriptional Responses to the Environment Group announced new findings in their study of the stalling of RNA polymerase II as it begins to transcribe a gene. The most recent findings complement earlier research demonstrating that the stalling (or pausing) of RNA polymerase is widespread throughout the genome. Researchers found that stalling could enhance gene expression by preventing epigenetic changes like the formation of repressive chromatin structures, and that stalling is important for regulation of mammalian immune response, including the critical inflammatory mediator TNF-alpha. The group developed tools to perform high-resolution mapping of stalled RNA polymerase complexes across the genome, using next-generation sequencing technologies. In addition to confirming the widespread regulation of genes by polymerase stalling, these studies reveal that DNA sequences in the promoter region influence pausing and RNA polymerase dynamics.
Muse GW, Gilchrist DA, Nechaev S, Shah R, Parker JS, Grissom SF, Zeitlinger J, Adelman K. 2007. RNA polymerase is poised for activation across the genome. Nat Genet 39(12):1507-1511. [Abstract] [Full Text]
Zeitlinger J, Stark A, Kellis M, Hong J-W, Nechaev S, Adelman K, Levine M, Young RA. 2007. RNA polymerase stalling at developmental control genes in the drosophila melanogaster embryo. Nat Genet 39(12):1512-1516. [Abstract] [Full Text]
Gilchrist DA, Nechaev S, Lee C, Gosh SKB, Collins J, Li L, Gilmour DS, Adelman K. 2008. NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly. Genes Dev 22(14):1921-1933. [Abstract] [Full Text]
Adelman K, Kennedy MA, Nechaev S, Gilchrist DA, Muse GW, Chinenov Y, Rogatsky I. 2009. Immediate mediators of the inflammatory response are poised for gene activation through RNA polymerase stalling. Proc Natl Acad Sci 106(43):18207-18212. [Abstract] [Full Text]
Nechaev S, Fargo DC, dos Santos G, Liu L, Gao Y, Adelman K. 2010. Global Analysis of Short RNAs Reveals Widespread Promoter-Proximal Stalling and Arrest of Pol II in Drosophila. Science 327(5963):335-338. [Abstract] [Full Text]
Environmental Factor article: