Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers
Open Access
- 10 November 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 46 (12), 1311-1320
- https://doi.org/10.1038/ng.3142
Abstract
John Lis, Adam Siepel and colleagues map transcription start sites across the genome in two human cell lines using a nuclear run-on protocol called GRO-cap. They find a common architecture of initiation at both promoters and enhancers and that transcript elongation stability provides the strongest distinction between promoters and enhancers. Despite the conventional distinction between them, promoters and enhancers share many features in mammals, including divergent transcription and similar modes of transcription factor binding. Here we examine the architecture of transcription initiation through comprehensive mapping of transcription start sites (TSSs) in human lymphoblastoid B cell (GM12878) and chronic myelogenous leukemic (K562) ENCODE Tier 1 cell lines. Using a nuclear run-on protocol called GRO-cap, which captures TSSs for both stable and unstable transcripts, we conduct detailed comparisons of thousands of promoters and enhancers in human cells. These analyses identify a common architecture of initiation, including tightly spaced (110 bp apart) divergent initiation, similar frequencies of core promoter sequence elements, highly positioned flanking nucleosomes and two modes of transcription factor binding. Post-initiation transcript stability provides a more fundamental distinction between promoters and enhancers than patterns of histone modification and association of transcription factors or co-activators. These results support a unified model of transcription initiation at promoters and enhancers.Keywords
This publication has 69 references indexed in Scilit:
- Condensin controls recruitment of RNA polymerase II to achieve nematode X-chromosome dosage compensationeLife, 2013
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- Landscape of transcription in human cellsNature, 2012
- U1 snRNP Determines mRNA Length and Regulates Isoform ExpressionCell, 2012
- Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription RegulationCell, 2012
- H3K4 tri-methylation provides an epigenetic signature of active enhancersThe EMBO Journal, 2011
- Finding distal regulatory elements in the human genomeCurrent Opinion in Genetics & Development, 2009
- Dynamic Regulation of Nucleosome Positioning in the Human GenomeCell, 2008
- Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genomeNature Genetics, 2007
- Expression of a β-globin gene is enhanced by remote SV40 DNA sequencesCell, 1981