Evidence map›Paper›PMID 31223115›Full record

ArticleeLife2019

Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity.

Jeehae Park, Javier Estrada, Gemma Johnson, Ben J Vincent, Chiara Ricci-Tam, Meghan Dj Bragdon, Yekaterina Shulgina, Anna Cha, Zeba Wunderlich, Jeremy Gunawardena and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

44 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
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  6. Emergence of activation or repression in transcriptional control under a fixed molecular context.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  17. Review
  18. InterpretingNature machine intelligence · 2024
    Article
  19. The Hill function is the universal Hopfield barrier for sharpness of input-output responses.Proceedings of the National Academy of Sciences of the United States of America · 2024
    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

11 authors at 1 institution in 1 country.

Jeehae ParkDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Javier EstradaDepartment of Systems Biology, Harvard Medical School, Boston, United States.ORCID 0000-0003-3646-204X
Gemma JohnsonDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Ben J VincentDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Chiara Ricci-TamDepartment of Systems Biology, Harvard Medical School, Boston, United States.ORCID 0000-0002-6549-1838
Meghan Dj BragdonDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Yekaterina ShulginaDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Anna ChaDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Zeba WunderlichDepartment of Systems Biology, Harvard Medical School, Boston, United States.
Jeremy GunawardenaDepartment of Systems Biology, Harvard Medical School, Boston, United States.ORCID 0000-0002-7280-1152
Angela H DePaceDepartment of Systems Biology, Harvard Medical School, Boston, United States.ORCID 0000-0001-5723-0438
Harvard University · US

Funding

Information Integration and Energy Expenditure in Eukaryotic Gene RegulationR01GM122928 · NIGMS · HARVARD MEDICAL SCHOOL · PI DEPACE, ANGELA H, GUNAWARDENA, JEREMY · 2017 to 2024
$3.7M
NIGMS NIH HHS R01 GM122928NIH HHS 5K99HD073191-02NIH HHS R01GM122928
6 · The paper itself

Abstract

Developmental enhancers integrate graded concentrations of transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd). We systematically interrogate cis and trans factors that influence the shape and position of expression driven by HbP2, and find that the prevailing model, based on pairwise cooperative binding of Bcd to HbP2 is not adequate. We demonstrate that other proteins, such as pioneer factors, Mediator and histone modifiers influence the shape and position of the HbP2 expression pattern. Comparing our results to theory reveals how higher-order cooperativity and energy expenditure impact boundary location and sharpness. Our results emphasize that the bacterial view of transcription regulation, where pairwise interactions between regulatory proteins dominate, must be reexamined in animals, where multiple molecular mechanisms collaborate to shape the gene regulatory function.

Indexed as

DrosophilaGene Expression Regulation, DevelopmentalAnimalsDNA-Binding ProteinsDrosophila ProteinsGene Expression ProfilingHomeodomain ProteinsModels, GeneticTrans-ActivatorsTranscription FactorsTranscription, Geneticbcd protein, DrosophilaDNA-Binding ProteinsDrosophila Proteinshb protein, DrosophilaHomeodomain ProteinsTrans-ActivatorsTranscription Factorschromosomescomputational biologyD. melanogasterDrosophilaenhancergene expressionsystems biologytranscription

Identifiers

PMID31223115
PMCPMC6588347
OpenAlexW2949687158

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.