Evidence map›Paper›PMID 33795867›Full record

ArticleNature genetics2021

Cis-regulatory chromatin loops arise before TADs and gene activation, and are independent of cell fate during early Drosophila development.

Sergio Martin Espinola, Markus Götz, Maelle Bellec, Olivier Messina, Jean-Bernard Fiche, Christophe Houbron, Matthieu Dejean, Ingolf Reim, Andrés M Cardozo Gizzi, Mounia Lagha and 1 more

Open access · bronzeAbstract read
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In one paragraph

Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
12.6field-weighted citation impact, top 1% 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

97 citing papers in PubMed, 180 citations in OpenAlex.

  1. Transcription and Three-Dimensional Genome Organization: Cause, Consequence, or Coordination?BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
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  5. TAD boundaries and gene activity are uncoupled.bioRxiv : the preprint server for biology · 2026
    Article
  6. Review
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  11. CTCF Mediates the Cis-Regulatory Hubs in Mouse Hearts.International journal of molecular sciences · 2025
    Article
  12. Review
  13. Article
  14. Article
  15. Article
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  17. Article
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37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Sergio Martin Espinola *Centre de Biologie Structurale, CNRS UMR 5048, INSERM U1054, Univ Montpellier, Montpellier, France.ORCID http://orcid.org/0000-0001-9000-2883
Markus Götz *Centre de Biologie Structurale, CNRS UMR 5048, INSERM U1054, Univ Montpellier, Montpellier, France.ORCID http://orcid.org/0000-0002-1956-7328
Maelle BellecIGMM, CNRS, Univ Montpellier, Montpellier, France.ORCID http://orcid.org/0000-0002-9029-0042
Olivier MessinaCentre de Biologie Structurale, CNRS UMR 5048, INSERM U1054, Univ Montpellier, Montpellier, France.
Jean-Bernard FicheCentre de Biologie Structurale, CNRS UMR 5048, INSERM U1054, Univ Montpellier, Montpellier, France.
Christophe HoubronCentre de Biologie Structurale, CNRS UMR 5048, INSERM U1054, Univ Montpellier, Montpellier, France.
Matthieu DejeanIGMM, CNRS, Univ Montpellier, Montpellier, France.
Ingolf ReimDepartment of Biology, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.ORCID http://orcid.org/0000-0001-8069-5532
Andrés M Cardozo GizziCentro de Investigación en Medicina Traslacional Severo Amuchastegui, Instituto Universitario de Ciencias Biomédicas de Córdoba, Consejo Nacional de Investigaciones Científicas y Técnicas, Córdoba, Argentina.ORCID http://orcid.org/0000-0003-3894-1845
Mounia LaghaIGMM, CNRS, Univ Montpellier, Montpellier, France. mounia.lagha@igmm.cnrs.fr.ORCID http://orcid.org/0000-0002-7082-1950
Marcelo NollmannCentre de Biologie Structurale, CNRS UMR 5048, INSERM U1054, Univ Montpellier, Montpellier, France. marcelo.nollmann@cbs.cnrs.fr.ORCID http://orcid.org/0000-0003-3339-2349
Centre National de la Recherche Scientifique · FRConsejo Nacional de Investigaciones Científicas y Técnicas · ARFriedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acquisition of cell fate is thought to rely on the specific interaction of remote cis-regulatory modules (CRMs), for example, enhancers and target promoters. However, the precise interplay between chromatin structure and gene expression is still unclear, particularly within multicellular developing organisms. In the present study, we employ Hi-M, a single-cell spatial genomics approach, to detect CRM-promoter looping interactions within topologically associating domains (TADs) during early Drosophila development. By comparing cis-regulatory loops in alternate cell types, we show that physical proximity does not necessarily instruct transcriptional states. Moreover, multi-way analyses reveal that multiple CRMs spatially coalesce to form hubs. Loops and CRM hubs are established early during development, before the emergence of TADs. Moreover, CRM hubs are formed, in part, via the action of the pioneer transcription factor Zelda and precede transcriptional activation. Our approach provides insight into the role of CRM-promoter interactions in defining transcriptional states, as well as distinct cell types.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsCell DifferentiationCell LineageChromatinDrosophila melanogasterDrosophila ProteinsEmbryo, NonmammalianEnhancer Elements, GeneticGene Expression ProfilingGenomicsNuclear ProteinsPromoter Regions, GeneticSingle-Cell AnalysisTranscription FactorsTranscription, GeneticChromatinDrosophila ProteinsNuclear ProteinsTranscription Factorszld protein, Drosophila

Identifiers

PMID33795867
OpenAlexW3144036649

What OpenQuestion holds

Textmetadata
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.