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Cited by 693Genomics and Chromatin DynamicsChromatin Remodeling and CancerEpigenetics and DNA Methylation

Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers

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Core, Leighton J, Martins, André L, Danko, Charles G, Waters, Colin T, Siepel, Adam, Lis, John T·2014·Nature Genetics
DOI 10.1038/ng.3142PMC PMC4254663
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Abstract

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.

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  • The majority of active enhancers are themselves transcribed, producing enhancer RNAs in a bi-directional manner.

    “The majority of active enhancers are themselves transcribed, producing enhancer RNAs (eRNAs) in a bi-directional manner [73–77].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [73]

    The Abstract says enhancer transcription is widespread and that eRNAs are produced bidirectionally. The Discussion also reports bidirectional initiation at thousands of enhancers. Neither passage establishes that a majority of active enhancers are transcribed; the nearly 80% figure in the Abstract concerns promoters, not enhancers. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Both active enhancers and promoters occupy nucleosome-free chromatin, bind RNAP and can be divergently transcribed.

    “Both active enhancers and promoters occupy nucleosome-free chromatin, bind RNAP and can be divergently transcribed [73, 236, 237].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [73]

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Sorted by citations

Authors
Core, L. J., Martins, A. L., Danko, C. G., Waters, C. T., Siepel, A., & Lis, J. T.
Affiliations
  • Harvard University (US)
  • Cornell University (US)
Corresponding author
  • Siepel, Adam
  • Lis, John T
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2014-11-10
Volume
46
Issue
12
Pages
1311-1320
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.3142
PMC
PMC4254663
OpenAlex
W2091533196
Cited by
693
References
9
Citations by year
2026: 36 · 2025: 49 · 2024: 44 · 2023: 49 · 2022: 57 · 2021: 99 · 2020: 64 · 2019: 78 · 2018: 65 · 2017: 57 · 2016: 47 · 2015: 45 · 2014: 1 · 2013: 1
FWCI
20.51
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • National Institutes of Health
  • National Human Genome Research Institute (HG0070707, R01HG007070)
  • National Institute of General Medical Sciences (R01GM025232, R37GM025232, GM-25232)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
transcription initiation, promoter, enhancers, transcription start sites, divergent transcription, nascent RNA, transcript stability, nucleosome positioning, core promoter elements, transcription factor binding, histone modifications, GM12878, K562 cells, mammalian gene regulation
MeSH terms
B-Lymphocytes, Binding Sites, Chromatin, Enhancer Elements, Genetic, Histones, Humans, Markov Chains, Models, Genetic, Nucleosomes, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, RNA, RNA Splicing, Transcription, Genetic, K562 Cells, Transcription Initiation Site

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