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Cited by 50Pluripotent Stem Cells ResearchGenomics and Chromatin DynamicsGene Regulatory Network Analysis

Interactions between pluripotency factors specify cis-regulation in embryonic stem cells

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Fiore, Chris, Cohen, Barak A.·2016·Genome Research
DOI 10.1101/gr.200733.115PMC PMC4889965
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Abstract

We investigated how interactions between pluripotency transcription factors (TFs) affect cis-regulation. We created hundreds of synthetic cis-regulatory elements (CREs) comprised of combinations of binding sites for pluripotency TFs and measured their expression in mouse embryonic stem (ES) cells. A thermodynamic model that incorporates interactions between TFs explains a large portion (72%) of the variance in expression of these CREs. These interactions include three favorable heterotypic interactions between TFs. The model also predicts an unfavorable homotypic interaction between TFs, helping to explain the observation that homotypic chains of binding sites express at low levels. We further investigated the expression driven by CREs comprised of homotypic chains of KLF4 binding sites. Our results suggest that KLF homologs make unique contributions to regulation by these CREs. We conclude that a specific set of interactions between pluripotency TFs plays a large role in setting the levels of expression driven by CREs in ES cells.

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  • Measuring enhancer activity of synthetic, systematically designed DNA sequences with TFBSs placed in an otherwise inert sequence context is an alternative way to study the cis-regulatory code.

    “An alternative way to study the cis-regulatory code is to measure the enhancer activity of synthetic, systematically designed DNA sequences, where TF binding sites (TFBSs) are placed in an otherwise inert sequence context.27,30,31,32,33,34”

    From Design principles of cell-state-specific enhancers in hematopoiesis (2025) · cites this paper as [30]

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Cited by

Sorted by citations

Authors
Fiore, C., & Cohen, B. A.
Affiliations
Washington University in St. Louis (US)
ORCID
Cohen, Barak A.
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2016-04-15
Volume
26
Issue
6
Pages
778-786
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
DOI
10.1101/gr.200733.115
PMC
PMC4889965
OpenAlex
W2337928212
Cited by
50
References
2
Citations by year
2026: 6 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 2
Type
posted content
Language
en
Open access
Licence
other-oa
Locations
  • Genome Research (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, other-oa)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Science Foundation (DGE-1143954)
  • National Institutes of Health (R01 HG006790-01, RO1 GM092910-02)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • 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
Keywords
pluripotency transcription factors, cis-regulation, cis-regulatory elements, transcription factor interaction, thermodynamic modeling, heterotypic interactions, homotypic interactions, KLF4, mouse embryonic stem cells, gene expression regulation
MeSH terms
Mouse Embryonic Stem Cells, Kruppel-Like Factor 4, Animals, Binding Sites, Cells, Cultured, Gene Expression Regulation, Models, Genetic, Regulatory Sequences, Nucleic Acid, Thermodynamics, Transcription Factors, Gene Library, Gene Expression, Mice, Kruppel-Like Transcription Factors

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