Evidence map›Paper›PMID 40015278›Full record

ArticleDevelopmental cell2025

Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development.

Shreeta Chakraborty, Nina Wenzlitschke, Matthew J Anderson, Ariel Eraso, Manon Baudic, Joyce J Thompson, Alicia A Evans, Lilly M Shatford-Adams, Raj Chari, Parirokh Awasthi and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Transcription and Three-Dimensional Genome Organization: Cause, Consequence, or Coordination?BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  2. Review
  3. Genome-wide absolute quantification of chromatin looping.Nature structural & molecular biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. TAD boundaries and gene activity are uncoupled.bioRxiv : the preprint server for biology · 2026
    Article
  10. Review
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Shreeta ChakrabortyUnit on Genome Structure and Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Nina WenzlitschkeUnit on Genome Structure and Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Matthew J AndersonGenetics of Vertebrate Development Section, Cancer and Developmental Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Ariel ErasoUnit on Genome Structure and Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Manon BaudicUnit on Genome Structure and Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Joyce J ThompsonUnit on Genome Structure and Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Alicia A EvansBioinformatics and Scientific Programming Core, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Lilly M Shatford-AdamsBioinformatics and Scientific Programming Core, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Raj ChariLaboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Parirokh AwasthiLaboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Ryan K DaleBioinformatics and Scientific Programming Core, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Mark LewandoskiGenetics of Vertebrate Development Section, Cancer and Developmental Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Timothy J PetrosUnit on Cellular and Molecular Neurodevelopment, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Pedro P RochaUnit on Genome Structure and Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA; National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: pedrorocha@nih.gov.

Funding

Genome 3D organization as a determinant of cell-fate decisionsZIAHD008975 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI ROCHA, PEDRO · 2018 to 2025
$10.4M
The Role of Fgf Signaling in Vertebrate DevelopmentZ01BC010338 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LEWANDOSKI, MARK · 2000 to 2008
$697k
Intramural NIH HHS Z01 BC010338Intramural NIH HHS ZIA HD008975NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003I
6 · The paper itself

Abstract

Chromatin domains delimited by CTCF can restrict the range of enhancer action. However, disruption of some domain boundaries results in mild gene dysregulation and phenotypes. We tested whether perturbing a domain with multiple developmental regulators would lead to more severe outcomes. We chose a domain with three FGF ligand genes-Fgf3, Fgf4, and Fgf15-that control different murine developmental processes. Heterozygous deletion of a 23.9-kb boundary defined by four CTCF sites led to ectopic interactions of the FGF genes with enhancers active in the brain and induced FGF expression. This caused orofacial clefts, encephalocele, and fully penetrant perinatal lethality. Loss of the single CTCF motif oriented toward the enhancers-but not the three toward the FGF genes-recapitulated these phenotypes. Our works shows that small sequence variants at particular domain boundaries can have a surprisingly outsized effect and must be considered as potential sources of gene dysregulation in development and disease.

Indexed as

CCCTC-Binding FactorChromatinEmbryonic DevelopmentFibroblast Growth FactorsGene Expression Regulation, DevelopmentalAnimalsEnhancer Elements, GeneticFemaleFibroblast Growth Factor 3Fibroblast Growth Factor 4MiceCCCTC-Binding FactorChromatinCtcf protein, mouseFibroblast Growth Factor 3Fibroblast Growth Factor 4Fibroblast Growth FactorsCTCFepigeneticsFGFgene regulationnuclear organization

Identifiers

PMID40015278
PMCPMC12237608

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.