Evidence map›Paper›PMID 31831055›Full record

ArticleGenome biology2019

CTCF modulates allele-specific sub-TAD organization and imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains.

David Llères, Benoît Moindrot, Rakesh Pathak, Vincent Piras, Mélody Matelot, Benoît Pignard, Alice Marchand, Mallory Poncelet, Aurélien Perrin, Virgile Tellier and 2 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
7.7field-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

62 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
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  13. An EED/PRC2-H19 Loop Regulates Cerebellar Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
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  19. Review
  20. Article

2 more citing papers are in PubMed but not listed here.

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

12 authors at 1 institution in 1 country.

David LlèresInstitute of Molecular Genetics of Montpellier (IGMM), University of Montpellier, CNRS, Montpellier, France.
Benoît MoindrotInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-sud and University Paris-Saclay, Gif-sur-Yvette, France.
Rakesh PathakInstitute of Molecular Genetics of Montpellier (IGMM), University of Montpellier, CNRS, Montpellier, France.
Vincent PirasInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-sud and University Paris-Saclay, Gif-sur-Yvette, France.
Mélody MatelotInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-sud and University Paris-Saclay, Gif-sur-Yvette, France.
Benoît PignardInstitute of Molecular Genetics of Montpellier (IGMM), University of Montpellier, CNRS, Montpellier, France.
Alice MarchandInstitute of Molecular Genetics of Montpellier (IGMM), University of Montpellier, CNRS, Montpellier, France.
Mallory PonceletInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-sud and University Paris-Saclay, Gif-sur-Yvette, France.
Aurélien PerrinInstitute of Molecular Genetics of Montpellier (IGMM), University of Montpellier, CNRS, Montpellier, France.
Virgile TellierInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-sud and University Paris-Saclay, Gif-sur-Yvette, France.
Robert FeilInstitute of Molecular Genetics of Montpellier (IGMM), University of Montpellier, CNRS, Montpellier, France. robert.feil@igmm.cnrs.fr.
Daan NoordermeerInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-sud and University Paris-Saclay, Gif-sur-Yvette, France. daan.noordermeer@i2bc.paris-saclay.fr.ORCID 0000-0002-9296-7002
Centre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGenomic imprinting is essential for mammalian development and provides a unique paradigm to explore intra-cellular differences in chromatin configuration. So far, the detailed allele-specific chromatin organization of imprinted gene domains has mostly been lacking. Here, we explored the chromatin structure of the two conserved imprinted domains controlled by paternal DNA methylation imprints-the Igf2-H19 and Dlk1-Dio3 domains-and assessed the involvement of the insulator protein CTCF in mouse cells.

resultsBoth imprinted domains are located within overarching topologically associating domains (TADs) that are similar on both parental chromosomes. At each domain, a single differentially methylated region is bound by CTCF on the maternal chromosome only, in addition to multiple instances of bi-allelic CTCF binding. Combinations of allelic 4C-seq and DNA-FISH revealed that bi-allelic CTCF binding alone, on the paternal chromosome, correlates with a first level of sub-TAD structure. On the maternal chromosome, additional CTCF binding at the differentially methylated region adds a further layer of sub-TAD organization, which essentially hijacks the existing paternal-specific sub-TAD organization. Perturbation of maternal-specific CTCF binding site at the Dlk1-Dio3 locus, using genome editing, results in perturbed sub-TAD organization and bi-allelic Dlk1 activation during differentiation.

conclusionsMaternal allele-specific CTCF binding at the imprinted Igf2-H19 and the Dlk1-Dio3 domains adds an additional layer of sub-TAD organization, on top of an existing three-dimensional configuration and prior to imprinted activation of protein-coding genes. We speculate that this allele-specific sub-TAD organization provides an instructive or permissive context for imprinted gene activation during development.

Indexed as

Genomic ImprintingAnimalsCalcium-Binding ProteinsCCCTC-Binding FactorInsulin-Like Growth Factor IIIodide PeroxidaseMiceRNA, Long NoncodingCalcium-Binding ProteinsCCCTC-Binding FactorCtcf protein, mouseDlk1 protein, mouseH19 long non-coding RNAIGF2 protein, mouseInsulin-Like Growth Factor IIIodide Peroxidaseiodothyronine deiodinase type IIIMEG3 non-coding RNA, mouseRNA, Long Noncoding3D genome organizationCTCFDevelopmentDlk1DNA methylationGenomic imprintingIgf2Meg3TADsTopologically associating domains

Identifiers

PMID31831055
PMCPMC6909504
OpenAlexW2984988759

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.