Cited by 101Genomics and Chromatin DynamicsChromatin Remodeling and CancerGene Regulatory Network Analysis

Systematic analysis of intrinsic enhancer-promoter compatibility in the mouse genome

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Martinez-Ara, Miguel, Comoglio, Federico, van Arensbergen, Joris, van Steensel, Bas·2022·Molecular Cell

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Abstract

Gene expression is in part controlled by cis-regulatory elements (CREs) such as enhancers and repressive elements. Anecdotal evidence has indicated that a CRE and a promoter need to be biochemically compatible for promoter regulation to occur, but this compatibility has remained poorly characterized in mammalian cells. We used high-throughput combinatorial reporter assays to test thousands of CRE-promoter pairs from three Mb-sized genomic regions in mouse cells. This revealed that CREs vary substantially in their promoter compatibility, ranging from striking specificity to broad promiscuity. More than half of the tested CREs exhibit significant promoter selectivity. Housekeeping promoters tend to have similar CRE preferences, but other promoters exhibit a wide diversity of compatibilities. Higher-order transcription factors (TF) motif combinations may account for compatibility. CRE-promoter selectivity does not correlate with looping interactions in the native genomic context, suggesting that chromatin folding and compatibility are two orthogonal mechanisms that confer specificity to gene regulation.

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Crossref · 10.1016/j.molcel.2022.04.009

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  • Different enhancers show various levels of specificity, ranging from the ability to activate a wide range of promoters to highly specific activation of a particular promoter.

    “Analysis of a number of enhancer-promoter pairs in the mouse genome has demonstrated that different enhancers show various levels of specificity, ranging from the ability to activate a wide range of promoters to highly specific activation of a particular promoter [136].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [136]

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  1. Kwon D. Mucci D. Langlais K.K. Americo J.L. Devido S.K. Cheng Y. Kassis J.A. Enhancer-promoter communication at the Drosophila engrailed locus Development 136 2009 3067 3075 19675130 PMC2730364

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Authors
Martinez-Ara, M., Comoglio, F., van Arensbergen, J., & van Steensel, B.
Affiliations
The Netherlands Cancer Institute (NL)
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2022-07
Volume
82
Issue
13
Pages
2519-2531.e6
ISSN
1097-2765 (ISSN-L)
OpenAlex
W4225797159
Cited by
101
References
75
Citations by year
2026: 15 · 2025: 23 · 2024: 24 · 2023: 27 · 2022: 12
FWCI
7.02
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (165206)
  • KWF Kankerbestrijding
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 › Gene Regulatory Network Analysis
Keywords
cis-regulatory elements, enhancers, promoter selectivity, transcription factor binding motifs, chromatin looping, chromatin folding, gene expression regulation, mouse genome
MeSH terms
Animals, Enhancer Elements, Genetic, Gene Expression Regulation, Mammals, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription Factors, Genome, Genomics, Mice

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