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Originally published in Science Express on 4 December 2008
Science 19 December 2008:
Vol. 322. no. 5909, pp. 1849 - 1851
DOI: 10.1126/science.1162253
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Reports

Divergent Transcription from Active Promoters

Amy C. Seila,1* J. Mauro Calabrese,1,2*{dagger} Stuart S. Levine,3 Gene W. Yeo,4{ddagger} Peter B. Rahl,3 Ryan A. Flynn,1 Richard A. Young,2,3 Phillip A. Sharp1,2§

Transcription initiation by RNA polymerase II (RNAPII) is thought to occur unidirectionally from most genes. Here, we present evidence of widespread divergent transcription at protein-encoding gene promoters. Transcription start site–associated RNAs (TSSa-RNAs) nonrandomly flank active promoters, with peaks of antisense and sense short RNAs at 250 nucleotides upstream and 50 nucleotides downstream of TSSs, respectively. Northern analysis shows that TSSa-RNAs are subsets of an RNA population 20 to 90 nucleotides in length. Promoter-associated RNAPII and H3K4-trimethylated histones, transcription initiation hallmarks, colocalize at sense and antisense TSSa-RNA positions; however, H3K79-dimethylated histones, characteristic of elongating RNAPII, are only present downstream of TSSs. These results suggest that divergent transcription over short distances is common for active promoters and may help promoter regions maintain a state poised for subsequent regulation.

1 Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
4 Salk Institute, Crick-Jacobs Center for Theoretical and Computational Biology, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Genetics and the Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA.

{ddagger} Present address: Department of Cellular and Molecular Medicine, University of California, San Diego, CA 92037, USA.

§ To whom correspondence should be addressed. E-mail: sharppa{at}mit.edu

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