Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells
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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.
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RNA Pol II ChIP on chip and ChIP-seq data showed that RNA Pol II accumulates on exons in yeast and human, suggesting that RNA Pol II pauses over exons.
“Indeed, RNA Pol II ChIP on chip and ChIP‐seq data showed that RNA Pol II accumulates on exons in yeast and human, suggesting that RNA Pol II pauses over exons (Brodsky et al, 2005; Schwartz et al, 2009; Alexander et al, 2010; Carrillo Oesterreich et al, 2010; Kwak et al, 2013; Mayer et al, 2015; Nojima et al, 2015; Harlen et al, 2016).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Brodsky et al, 2005
The Results and discussion report RNA polymerase II enrichment at exons in human HeLa cells and say the pattern is consistent with transcriptional pausing, while acknowledging another possible explanation. This paper used ChIP with tiled microarrays, not ChIP-seq; it also describes Pol II enrichment in yeast genes as more uniform rather than establishing exon accumulation there. (LLM, conf=0.88)
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“…Pol II ChIP on chip and ChIP-seq data showed that RNA Pol II accumulates on exons in yeast and human, suggesting that RNA Pol II pauses over exons (Brodsky et al , 2005; Schwartz et al , 2009; Alexander et al , 2010; Carrillo Oesterreich et al , 2010; Kwak et al , 2013; Mayer et al , 2015; Nojima…”
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- Authors
- Brodsky, A. S., Meyer, C. A., Swinburne, I. A., Hall, G., Keenan, B. J., Liu, X. S., Fox, E. A., & Silver, P. A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Brodsky, Alexander S
- Venue
- Genome Biology
- Published
- 2005-07-15
- Volume
- 6
- Issue
- 8
- Pages
- R64-R64
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC1273631
- OpenAlex
- W2117170199
- Cited by
- 94
- References
- 29
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 7 · 2014: 3 · 2013: 1 · 2012: 7
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- U.S. Department of Defense
- Dana-Farber Cancer Institute
- National Human Genome Research Institute (K22 HG02488-01A1, K22HG002488)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- RNA polymerase II, co-transcriptional regulation, transcription elongation, alternative splicing, promoter, pre-mRNA processing, transcription initiation, transcription termination, ENCODE, human genome
- MeSH terms
- Chromosome Mapping, Chromosomes, Human, Exons, Gene Expression Regulation, HeLa Cells, Humans, RNA Polymerase II, RNA Polymerase III, RNA, Messenger, Transcription, Genetic, Genome, Human, Chromatin Immunoprecipitation
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