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Cited by 1,639Genomics and Chromatin DynamicsChromatin Remodeling and CancerEpigenetics and DNA Methylation

ChIP-seq accurately predicts tissue-specific activity of enhancers

Open access
Visel, Axel, Blow, Matthew J., Li, Zirong, Zhang, Tao, Akiyama, Jennifer A., Holt, Amy, Plajzer-Frick, Ingrid, Shoukry, Malak +6 more·2009·Nature
DOI 10.1038/nature07730PMC PMC2745234
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Abstract

A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

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  • Histone modification and cofactor binding are enriched but not completely predictive of enhancer activity.

    “Although enriched, histone modification and cofactor binding is not completely predictive of enhancer activity54,58,72,77,105.”

    From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [54]

    The Discussion reports that p300 cofactor binding predicted tissue-specific enhancer activity in 80% of tested cases, supporting enrichment without perfect prediction. The paper does not establish the same claim for histone modifications; its Discussion mentions epigenetic marks generally but does not test their predictive accuracy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Enhancer detection based on chromatin profiling may falsely detect regions without appreciable regulatory activity, as well as miss some functional elements.

    “While enhancer detection based on chromatin profiling has become standard, this approach may falsely detect regions without appreciable regulatory activity, as well as miss some functional elements [146, 162].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [146]

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Authors
Visel, A., Blow, M. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., Afzal, V., Ren, B., Rubin, E. M., & Pennacchio, L. A.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • University of California San Diego (US)
  • Joint Genome Institute (US)
Corresponding author
Pennacchio, Len A.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2009-02-01
Volume
457
Issue
7231
Pages
854-858
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature07730
PMC
PMC2745234
OpenAlex
W1595665778
Cited by
1,639
References
7
Citations by year
2026: 22 · 2025: 34 · 2024: 57 · 2023: 55 · 2022: 60 · 2021: 76 · 2020: 91 · 2019: 94 · 2018: 99 · 2017: 74 · 2016: 108 · 2015: 139 · 2014: 144 · 2013: 158 · 2012: 150
FWCI
57.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • University of North Texas Digital Library (University of North Texas) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Lawrence Berkeley National Laboratory
Funders
  • National Human Genome Research Institute (R01HG003988)
  • National Institute of Neurological Disorders and Stroke (R01NS062859)
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
enhancers, P300, enhancer activity prediction, tissue-specific enhancers, ChIP-seq, embryonic forebrain, midbrain, limb development, mouse embryo
MeSH terms
p300-CBP-Associated Factor, Animals, Chromosome Mapping, Embryo, Mammalian, Extremities, Mesencephalon, Prosencephalon, Conserved Sequence, Gene Expression Regulation, Developmental, Chromatin Immunoprecipitation, p300-CBP Transcription Factors, Mice

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