The DOI matches its Crossref record; 74 of the 75 references it cites were found in a registry or an index.
Systematic analysis of intrinsic enhancer-promoter compatibility in the mouse genome
Open accessPublished version of a preprint
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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“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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Integration by parts: The multi-layered mechanisms of cis-regulatory control
Cornwall-Scoones, J., Briscoe, J., & Delàs, M. J. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.09.016
Metadata
- Authors
- Martinez-Ara, M., Comoglio, F., van Arensbergen, J., & van Steensel, B.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Corresponding author
- van Steensel, Bas
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 82
- Issue
- 13
- Pages
- 2519-2531.e6
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC9278412
- 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
- hybrid
- doi.org
- Licence
- 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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