Signaling pathways differentially affect RNA polymerase II initiation, pausing, and elongation rate in cells

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:	Siepel, Adam
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:	Publisher
URI:	https://repository.cshl.edu/id/eprint/31059

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