The Shh Topological Domain Facilitates the Action of Remote Enhancers by Reducing the Effects of Genomic Distances
Open accessAbstract
Gene expression often requires interaction between promoters and distant enhancers, which occur within the context of highly organized topologically associating domains (TADs). Using a series of engineered chromosomal rearrangements at the Shh locus, we carried out an extensive fine-scale characterization of the factors that govern the long-range regulatory interactions controlling Shh expression. We show that Shh enhancers act pervasively, yet not uniformly, throughout the TAD. Importantly, changing intra-TAD distances had no impact on Shh expression. In contrast, inversions disrupting the TAD altered global folding of the region and prevented regulatory contacts in a distance-dependent manner. Our data indicate that the Shh TAD promotes distance-independent contacts between distant regions that would otherwise interact only sporadically, enabling functional communication between them. In large genomes where genomic distances per se can limit regulatory interactions, this function of TADs could be as essential for gene expression as the formation of insulated neighborhoods.
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Analysis in the Shh locus suggests that within-TAD chromosomal contacts do not show a pronounced distance dependence.
“analysis in the Shh locus suggests that within-TAD chromosomal contacts there do not show a pronounced distance dependence [467].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [467]
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- Authors
- Symmons, O., Pan, L., Remeseiro, S., Aktas, T., Klein, F., Huber, W., & Spitz, F.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Spitz, François
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 39
- Issue
- 5
- Pages
- 529-543
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC5142843
- OpenAlex
- W2551543748
- Cited by
- 222
- References
- 21
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 19 · 2023: 25 · 2022: 20 · 2021: 32 · 2020: 29 · 2019: 29 · 2018: 24 · 2017: 19 · 2016: 1
- FWCI
- 12.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Developmental Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Louis-Jeantet Foundation
- Marie Curie Actions COFUND
- European Molecular Biology Laboratory
- Deutsche Forschungsgesellschaft (SP 1331/3-1)
- 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 › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- Sonic hedgehog, topologically associating domains, long-range enhancer-promoter interactions, chromatin looping, chromosomal inversions, chromatin folding, chromatin insulation, gene expression regulation
- MeSH terms
- Congenital Abnormalities, Animals, Enhancer Elements, Genetic, Mice, Inbred C57BL, Mice, Transgenic, Promoter Regions, Genetic, Gene Expression Regulation, Developmental, Mice, Gene Regulatory Networks, Hedgehog Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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