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Cited by 17Genomics and Chromatin DynamicsGene Regulatory Network AnalysisDevelopmental Biology and Gene Regulation

A sequence level model of an intact locus predicts the location and function of nonadditive enhancers

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Barr, Kenneth A., Reinitz, John·2017·PLOS ONE
DOI 10.1371/journal.pone.0180861PMC PMC5513433
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Abstract

Metazoan gene expression is controlled through the action of long stretches of noncoding DNA that contain enhancers-shorter sequences responsible for controlling a single aspect of a gene's expression pattern. Models built on thermodynamics have shown how enhancers interpret protein concentration in order to determine specific levels of gene expression, but the emergent regulatory logic of a complete regulatory locus shows qualitative and quantitative differences from isolated enhancers. Such differences may arise from steric competition limiting the quantity of DNA that can simultaneously influence the transcription machinery. We incorporated this competition into a mechanistic model of gene regulation, generated efficient algorithms for this computation, and applied it to the regulation of Drosophila even-skipped (eve). This model finds the location of enhancers and identifies which factors control the boundaries of eve expression. This model predicts a new enhancer that, when assayed in vivo, drives expression in a non-eve pattern. Incorporation of chromatin accessibility eliminates this inconsistency.

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  • Under common biophysical assumptions, increases in motif number and affinity lead to higher TF occupancy.

    “Under common biophysical assumptions, increases in these two quantities lead to higher TF occupancy.46,47”

    From Design principles of cell-state-specific enhancers in hematopoiesis (2025) · cites this paper as [47]

    The Results section (‘Sequence level model without enhancer competition and eve expression’; page unavailable) says the model calculates equilibrium TF occupancy from DNA sequence and binding preferences. Materials and methods (‘Parameter estimation’; page unavailable) links binding scores to relative affinity. But the passages on binding-site number discuss the computational cost of calculating occupancy, not whether adding sites raises it; our copy does not state the claimed increase in occupancy from increasing either quantity. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

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Sorted by citations

Authors
Barr, K. A., & Reinitz, J.
Affiliations
University of Chicago (US)
Corresponding author
Barr, Kenneth A.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-07-17
Volume
12
Issue
7
Pages
e0180861
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0180861
PMC
PMC5513433
OpenAlex
W2735001713
Cited by
17
References
4
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 1
FWCI
0.78
Type
journal article
Language
en
Update notices
correction (2018-05-07)
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • University of Chicago (cc-by)
Funders
  • National Institutes of Health (R01 OD010936)
  • University of Chicago
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
chromatin accessibility, non-coding DNA, transcriptional regulation
MeSH terms
Animals, Chromatin, DNA, DNA-Binding Proteins, Drosophila, Enhancer Elements, Genetic, Models, Genetic, RNA, Messenger, Transcription Factors, Drosophila Proteins, STAT Transcription Factors, Genetic Loci

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