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Cited by 87Retinal Development and DisordersGenomics and Chromatin DynamicsGene Regulatory Network Analysis

A Simple Grammar Defines Activating and Repressing cis-Regulatory Elements in Photoreceptors

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White, Michael A., Kwasnieski, Jamie C., Myers, Connie A., Shen, Susan Q., Corbo, Joseph C., Cohen, Barak A.·2016·Cell Reports
DOI 10.1016/j.celrep.2016.09.066PMC PMC5123866
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Abstract

Transcription factors often activate and repress different target genes in the same cell. How activation and repression are encoded by different arrangements of transcription factor binding sites in cis -regulatory elements is poorly understood. We investigated how sites for the transcription factor CRX encode both activation and repression in photoreceptors by assaying thousands of genomic and synthetic cis -regulatory elements in wild-type and Crx −/− retinas. We found that sequences with high affinity for CRX repress transcription, whereas sequences with lower affinity activate. This rule is modified by a cooperative interaction between CRX sites and sites for the transcription factor NRL, which overrides the repressive effect of high affinity for CRX. Our results show how simple rearrangements of transcription factor binding sites encode qualitatively different responses to a single transcription factor and explain how CRX plays multiple cis -regulatory roles in the same cell.

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  • Experimental manipulations of TF levels or mutagenesis of natural enhancers demonstrate that single TFs cause non-trivial increases and decreases of the activity of TF-bound enhancers.

    “Experimental manipulations of TF levels24,25,26 or mutagenesis of natural enhancers27 demonstrate that single TFs cause non-trivial increases and decreases of the activity of TF-bound enhancers”

    From Design principles of cell-state-specific enhancers in hematopoiesis (2025) · cites this paper as [27]

  • 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.

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    From Design principles of cell-state-specific enhancers in hematopoiesis (2025) · cites this paper as [27]

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Cited by

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Authors
White, M. A., Kwasnieski, J. C., Myers, C. A., Shen, S. Q., Corbo, J. C., & Cohen, B. A.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Cohen, Barak A.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2016-10
Volume
17
Issue
5
Pages
1247-1254
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2016.09.066
PMC
PMC5123866
OpenAlex
W2536763320
Cited by
87
References
2
Citations by year
2026: 4 · 2025: 13 · 2024: 16 · 2023: 13 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 3 · 2018: 11 · 2017: 7
FWCI
2.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
NIH (HG006346, GM092910)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • 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
cis-regulatory elements, transcriptional activation, transcriptional repression, photoreceptors, retinal development
MeSH terms
Animals, Base Sequence, Binding Sites, Eye Proteins, Mice, Inbred C57BL, Photoreceptor Cells, Promoter Regions, Genetic, Protein Binding, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Trans-Activators, Genome, Homeodomain Proteins, Basic-Leucine Zipper Transcription Factors

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