Danko, C. G., Hah, N., Luo, X., Martins, A. L., Core, L., Lis, J. T., Siepel, A., Kraus, W. L.
(April 2013)
Signaling pathways differentially affect RNA polymerase II initiation, pausing, and elongation rate in cells.
Mol Cell, 50 (2).
pp. 212-22.
ISSN 1097-2765
Abstract
RNA polymerase II (Pol II) transcribes hundreds of kilobases of DNA, limiting the production of mRNAs and lncRNAs. We used global run-on sequencing (GRO-seq) to measure the rates of transcription by Pol II following gene activation. Elongation rates vary as much as 4-fold at different genomic loci and in response to two distinct cellular signaling pathways (i.e., 17beta-estradiol [E2] and TNF-alpha). The rates are slowest near the promoter and increase during the first ~15 kb transcribed. Gene body elongation rates correlate with Pol II density, resulting in systematically higher rates of transcript production at genes with higher Pol II density. Pol II dynamics following short inductions indicate that E2 stimulates gene expression by increasing Pol II initiation, whereas TNF-alpha reduces Pol II residence time at pause sites. Collectively, our results identify previously uncharacterized variation in the rate of transcription and highlight elongation as an important, variable, and regulated rate-limiting step during transcription.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
Estradiol/pharmacology/physiology
Humans
Kinetics
MCF-7 Cells
Promoter Regions, Genetic
RNA Polymerase II/*metabolism/physiology
RNA, Messenger/*biosynthesis/genetics
*Signal Transduction
Transcription Factors/metabolism
Transcription Initiation Site
*Transcription Initiation, Genetic
Transcription, Genetic
Transcriptional Activation
Transcriptome
Tumor Necrosis Factor-alpha/pharmacology/physiology |
| Subjects: |
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > RNA polymerase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation > transduction
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation > transduction |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Siepel lab |
| Depositing User: |
Matt Covey
|
| Date: |
25 April 2013 |
| Date Deposited: |
15 Jan 2015 15:06 |
| Last Modified: |
15 Jan 2015 15:06 |
| PMCID: |
PMC3640649 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/31059 |
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