Evidence map›Paper›PMID 25252942›Full record

ArticleDevelopment (Cambridge, England)2014

Mapping the Shh long-range regulatory domain.

Eve Anderson, Paul S Devenney, Robert E Hill, Laura A Lettice

Abstract read
In one paragraph

Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Convergence of external and internal stressors on a stress-responsive enhancer of theProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Review
  6. Article
  7. The Direct and Individual Transcriptional Function of the Human Homodimeric and Heterodimeric Basic Helix-Loop-Helix Transcription Factors E47 and Scleraxis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. What is an enhancer?BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Review
  17. Article
  18. Integrative approaches to study enhancer-promoter communication.Current opinion in genetics & development · 2023
    Review
  19. Article
  20. The role of timing in the development and evolution of the limb.Frontiers in cell and developmental biology · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Eve AndersonMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.
Paul S DevenneyMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.
Robert E HillMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK bob.hill@igmm.ed.ac.uk.
Laura A LetticeMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.

Funding

Medical Research Council MC_PC_U127584494Medical Research Council MC_U127584494
6 · The paper itself

Abstract

Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity. We found that enhancer activities are retained inside a genomic region that corresponds to the topological associated domain (TAD) defined by Hi-C. This domain of approximately 900 kb is in an open conformation over its length and is generally susceptible to all Shh enhancers. Similar to the distal enhancers, an enhancer residing within the Shh second intron activates the reporter gene located at distances of hundreds of kilobases away, suggesting that both proximal and distal enhancers have the capacity to survey the Shh topological domain to recognise potential promoters. The widely expressed Rnf32 gene lying within the Shh domain evades enhancer activities by a process that may be common among other housekeeping genes that reside in large regulatory domains. Finally, the boundaries of the Shh TAD do not represent the absolute expression limits of enhancer activity, as expression activity is lost stepwise at a number of genomic positions at the verges of these domains.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsBlastocystDNA Transposable ElementsEnhancer Elements, GeneticGene Expression ProfilingGenes, ReporterGenetic Complementation TestHedgehog ProteinsHeterozygoteIntronsMiceMice, TransgenicModels, GeneticPromoter Regions, GeneticProtein Structure, TertiaryDNA Transposable ElementsHedgehog ProteinsShh protein, mouseEnhancersLong-range regulationMouseSleeping beauty transposonSonic hedgehog (Shh)Topological domains

Identifiers

PMID25252942
PMCPMC4197689

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.