Evidence map›Paper›PMID 36626871›Full record

ArticleDevelopmental cell2023

Enhancer architecture and chromatin accessibility constrain phenotypic space during Drosophila development.

Rafael Galupa, Gilberto Alvarez-Canales, Noa Ottilie Borst, Timothy Fuqua, Lautaro Gandara, Natalia Misunou, Kerstin Richter, Mariana R P Alves, Esther Karumbi, Melinda Liu Perkins and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Developmental cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
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

34 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Emergence Biases in Molecular Evolution.Genome biology and evolution · 2026
    Review
  6. Article
  7. Review
  8. Article
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  16. Article
  17. AntagonizingProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Review
  19. Chromatin enables precise and scalable gene regulation with factors of limited specificity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article
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

13 authors at 3 institutions in 2 countries.

Rafael GalupaEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany. Electronic address: rafael.galupa@embl.de.
Gilberto Alvarez-CanalesEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Noa Ottilie BorstEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Timothy FuquaEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Lautaro GandaraEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Natalia MisunouEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Kerstin RichterEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Mariana R P AlvesEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Esther KarumbiEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Melinda Liu PerkinsEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Tin KocijanEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Christine A RushlowDepartment of Biology, New York University, New York, NY 10003, USA.
Justin CrockerEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany. Electronic address: justin.crocker@embl.de.
European Molecular Biology Laboratory · DEEuropean Molecular Biology Organization · DENew York University · US

Funding

Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Annette L. Parks · 2014 to 2026
$13.5M
Regulation of zygotic genome activation by ZeldaR01GM063024 · NIGMS · NEW YORK UNIVERSITY · PI RUSHLOW, CHRISTINE A · 2002 to 2020
$5.2M
NIGMS NIH HHS R01 GM063024NIH HHS P40 OD018537
6 · The paper itself

Abstract

Developmental enhancers bind transcription factors and dictate patterns of gene expression during development. Their molecular evolution can underlie phenotypical evolution, but the contributions of the evolutionary pathways involved remain little understood. Here, using mutation libraries in Drosophila melanogaster embryos, we observed that most point mutations in developmental enhancers led to changes in gene expression levels but rarely resulted in novel expression outside of the native pattern. In contrast, random sequences, often acting as developmental enhancers, drove expression across a range of cell types; random sequences including motifs for transcription factors with pioneer activity acted as enhancers even more frequently. Our findings suggest that the phenotypic landscapes of developmental enhancers are constrained by enhancer architecture and chromatin accessibility. We propose that the evolution of existing enhancers is limited in its capacity to generate novel phenotypes, whereas the activity of de novo elements is a primary source of phenotypic novelty.

Indexed as

DrosophilaDrosophila ProteinsAnimalsChromatinDrosophila melanogasterEnhancer Elements, GeneticEvolution, MolecularGene Expression Regulation, DevelopmentalPhenotypeTranscription FactorsChromatinDrosophila ProteinsTranscription FactorsdevelopmentDrosophila melanogasterenhancersevolutiongene regulationnovel expression patternsphenotypical noveltiespioneer factorsrandom sequencesreporter assays

Identifiers

PMID36626871
PMCPMC9860173
OpenAlexW4313888339

What OpenQuestion holds

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LicenceCC BY
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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.