Functional maps of a genomic locus reveal confinement of an enhancer by its target gene
Open accessPreprint — published as 10.1126/science.ads6552
Abstract
Genes are often activated by enhancers located at large genomic distances. The importance of this positioning is poorly understood. By relocating promoter-reporter constructs into >1,000 alternative positions within a single locus, we dissected the positional relationship between the mouse Sox2 gene and its distal enhancer. This revealed an intricate, sharply confined activation landscape, in which the native Sox2 gene occupies an optimal position for its activation. Deletion of the gene relaxes this confinement and broadly increases reporter activity. Surprisingly, the confining effect of the Sox2 gene is partially conferred by its ∼1 kb coding region. Our local relocation approach provides high-resolution functional maps of a genomic locus and reveals that a gene can strongly constrain the realm of influence of its enhancer.
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Other specificities of the Sox2 locus, such as the ability of the coding sequence to engage in unusually strong interactions and constrain the regulatory inputs of the SCR, make SRR2 especially effective at supporting cohesin-independent regulation at Sox2.
“We suspect that other specificities of the Sox2 locus, such as the ability of the coding sequence to engage in unusually strong interactions (54) and constrain the regulatory inputs of the SCR (55), make SRR2 especially effective at supporting cohesin-independent regulation at Sox2.”
From Synergy between regulatory elements can render cohesin dispensable for distal enhancer function (2026) · cites this paper as [55]
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Synergy between regulatory elements can render cohesin dispensable for distal enhancer function
Hansen, K. L., Adachi, A. S., Braccioli, L., Kadvani, S., Boileau, R. M., Martinovic, M., Pokorny, B., Shah, R., Anderson, E. C., Zhang, K., et al. (2026) · Science · doi:10.1126/science.adt4221 · Cited by 29 · see citing works
- Authors
- Eder, M., Moene, C. J. I., Dauban, L., Leemans, C., & van Steensel, B.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Eder, Mathias
- Moene, Christina J.I.
- Venue
- Science
- Publisher
- openRxiv
- Published
- 2024-08-26
- Volume
- 389
- Issue
- 6766
- Pages
- eads6552-eads6552
- ISSN
- 0036-8075 (ISSN-L)
- PMC
- PMC7618358
- OpenAlex
- W4414321788
- Cited by
- 28
- References
- 0
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 3
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.C.222.049)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- distal enhancers, SOX2, promoter-reporter constructs, gene activation, enhancer deletion
- MeSH terms
- Animals, Enhancer Elements, Genetic, Promoter Regions, Genetic, Transcriptional Activation, Gene Deletion, Genes, Reporter, Mice, SOXB1 Transcription Factors, Genetic Loci
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