Evidence map›Paper›PMID 33398174›Full record

ArticleNature structural & molecular biology2021

Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation.

Naoki Kubo, Haruhiko Ishii, Xiong Xiong, Simona Bianco, Franz Meitinger, Rong Hu, James D Hocker, Mattia Conte, David Gorkin, Miao Yu and 6 more

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
209citing papers in PubMed, 1 pooled it
18.2field-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

209 citing papers in PubMed, 1 synthesis or guideline pooled it, 294 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. 3D Genome Engineering Using CRISPR/dCas Systems.International journal of molecular sciences · 2026
    Review
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149 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

16 authors at 8 institutions in 5 countries.

Naoki KuboDepartment of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
Haruhiko IshiiDepartment of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
Xiong XiongDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Simona BiancoDipartimento di Fisica, Università di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy.ORCID http://orcid.org/0000-0001-5819-060X
Franz MeitingerDepartment of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-8635-9078
Rong HuDepartment of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
James D HockerDepartment of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
Mattia ConteDipartimento di Fisica, Università di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy.ORCID http://orcid.org/0000-0002-6670-9800
David GorkinDepartment of Cellular and Molecular Medicine, Center for Epigenomics, University of California San Diego School of Medicine, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4944-4107
Miao YuDepartment of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
Bin LiDepartment of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
Jesse R DixonSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-6273-2181
Ming HuDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Mario NicodemiDipartimento di Fisica, Università di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy.ORCID http://orcid.org/0000-0002-8416-6416
Huimin ZhaoDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0002-9069-6739
Bing RenDepartment of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA. biren@ucsd.edu.ORCID http://orcid.org/0000-0002-5435-1127
University of California San Diego · USIstituto Nazionale di Fisica Nucleare, Sezione di Napoli · ITUniversity of Illinois Urbana-Champaign · USCleveland Clinic · USFudan University · CNLudwig Cancer Research · BEMax Delbrück Center · DESalk Institute for Biological Studies · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
Generation of novel cell type specific mouse genetic toolsU19MH114830 · NIMH · ALLEN INSTITUTE · PI NGAI, JOHN J. · 2017 to 2021
$64.7M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
San Diego Center for 4D Nucleome ResearchU54DK107977 · NIDDK · LUDWIG INSTITUTE FOR CANCER RES LTD · PI MURRE, CORNELIS, REN, BING · 2015 to 2019
$9.4M
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
Mapping Technology DevelopmentU54DK107965 · NIDDK · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI BELMONT, ANDREW STEVEN · 2015 to 2019
$8.6M
Center for Integrated Multi-modal and Multi-scale Nucleome ResearchUM1HG011585 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DULAC, CATHERINE, LEIN, ED · 2020 to 2024
$6.7M
NCI NIH HHS P30 CA014195NHGRI NIH HHS UM1 HG011585NIDDK NIH HHS U54 DK107965NIDDK NIH HHS U54 DK107977NIGMS NIH HHS T32 GM007198NIGMS NIH HHS T32 GM008666NIMH NIH HHS U19 MH114830
6 · The paper itself

Abstract

The CCCTC-binding factor (CTCF) works together with the cohesin complex to drive the formation of chromatin loops and topologically associating domains, but its role in gene regulation has not been fully defined. Here, we investigated the effects of acute CTCF loss on chromatin architecture and transcriptional programs in mouse embryonic stem cells undergoing differentiation to neural precursor cells. We identified CTCF-dependent enhancer-promoter contacts genome-wide and found that they disproportionately affect genes that are bound by CTCF at the promoter and are dependent on long-distance enhancers. Disruption of promoter-proximal CTCF binding reduced both long-range enhancer-promoter contacts and transcription, which were restored by artificial tethering of CTCF to the promoter. Promoter-proximal CTCF binding is correlated with the transcription of over 2,000 genes across a diverse set of adult tissues. Taken together, the results of our study show that CTCF binding to promoters may promote long-distance enhancer-dependent transcription at specific genes in diverse cell types.

Indexed as

AnimalsBinding SitesCCCTC-Binding FactorCell LineChromatinEnhancer Elements, GeneticGene Expression RegulationMiceMouse Embryonic Stem CellsNeural Stem CellsPromoter Regions, GeneticProtein BindingTranscriptional ActivationCCCTC-Binding FactorChromatinCtcf protein, mouse

Identifiers

PMID33398174
PMCPMC7913465
OpenAlexW3120280701

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.