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Science 319 (5871): 1791-1792

Copyright © 2008 by the American Association for the Advancement of Science

Transcription Regulation Through Promoter-Proximal Pausing of RNA Polymerase II

Leighton J. Core, and John T. Lis*

Abstract: Recent work has shown that the RNA polymerase II enzyme pauses at a promoter-proximal site of many genes in Drosophila and mammals. This rate-limiting step occurs after recruitment and initiation of RNA polymerase II at a gene promoter. This stage in early elongation appears to be an important and broadly used target of gene regulation.

Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.

* To whom correspondence should be addressed. E-mail: jtl10{at}

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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