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Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells

Alexander S Brodsky1*, Clifford A Meyer2, Ian A Swinburne1, Giles Hall3, Benjamin J Keenan1, Xiaole S Liu2, Edward A Fox3 and Pamela A Silver1

Author Affiliations

1 Department of Systems Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA

2 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02155, USA

3 Department of Medicine, Harvard Medical School and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA

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Genome Biology 2005, 6:R64  doi:10.1186/gb-2005-6-8-r64

Published: 15 July 2005

Abstract

Background

Transcription by RNA polymerase II is regulated at many steps including initiation, promoter release, elongation and termination. Accumulation of RNA polymerase II at particular locations across genes can be indicative of sites of regulation. RNA polymerase II is thought to accumulate at the promoter and at sites of co-transcriptional alternative splicing where the rate of RNA synthesis slows.

Results

To further understand transcriptional regulation at a global level, we determined the distribution of RNA polymerase II within regions of the human genome designated by the ENCODE project. Hypophosphorylated RNA polymerase II localizes almost exclusively to 5' ends of genes. On the other hand, localization of total RNA polymerase II reveals a variety of distinct landscapes across many genes with 74% of the observed enriched locations at exons. RNA polymerase II accumulates at many annotated constitutively spliced exons, but is biased for alternatively spliced exons. Finally, RNA polymerase II is also observed at locations not in gene regions.

Conclusion

Localizing RNA polymerase II across many millions of base pairs in the human genome identifies novel sites of transcription and provides insights into the regulation of transcription elongation. These data indicate that RNA polymerase II accumulates most often at exons during transcription. Thus, a major factor of transcription elongation control in mammalian cells is the coordination of transcription and pre-mRNA processing to define exons.