Pausing of RNA Polymerase II Disrupts DNA-Specified Nucleosome Organization to Enable Precise Gene Regulation

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.10.004 Byline: Daniel A. Gilchrist (1), Gilberto Dos Santos (1), David C. Fargo (2), Bin Xie (4), Yuan Gao (4)(5), Leping Li (3), Karen Adelman (1) Abstract: Metazoan transcription is controlled through either coordinated recruitment of transcription machinery to the gene promoter or regulated pausing of RNA polymerase II (Pol II) in early elongation. We report that a striking difference between genes that use these distinct regulatory strategies lies in the 'default' chromatin architecture specified by their DNA sequences. Pol II pausing is prominent at highly regulated genes whose sequences inherently disfavor nucleosome formation within the gene but favor occlusion of the promoter by nucleosomes. In contrast, housekeeping genes that lack pronounced Pol II pausing show higher nucleosome occupancy downstream, but their promoters are deprived of nucleosomes regardless of polymerase binding. Our results indicate that a key role of paused Pol II is to compete with nucleosomes for occupancy of highly regulated promoters, thereby preventing the formation of repressive chromatin architecture to facilitate further or future gene activation. Author Affiliation: (1) Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA (2) Library and Information Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA (3) Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA (4) Division of Genomics, Epigenomics and Bioinformatics, Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA (5) Neurogeneration and Stem Cell Biology Program, Institute of Cell Engineering, Johns Hopkins University, Baltimore, MD 21205, USA Article History: Received 21 May 2010; Revised 18 August 2010; Accepted 27 September 2010 Article Note: (miscellaneous) Published: November 11, 2010