Evidence map›Paper›PMID 34002095›Full record

ArticleNature genetics2021

CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains.

Hui Huang, Quan Zhu, Adam Jussila, Yuanyuan Han, Bogdan Bintu, Colin Kern, Mattia Conte, Yanxiao Zhang, Simona Bianco, Andrea M Chiariello and 8 more

Open access · greenAbstract read
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 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
11.6field-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

139 citing papers in PubMed, 191 citations in OpenAlex.

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  12. Genome-wide absolute quantification of chromatin looping.Nature structural & molecular biology · 2026
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79 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

18 authors at 7 institutions in 4 countries.

Hui HuangLudwig Institute for Cancer Research, La Jolla, CA, USA.
Quan ZhuCenter for Epigenomics, Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Adam JussilaLudwig Institute for Cancer Research, La Jolla, CA, USA.
Yuanyuan HanCenter for Epigenomics, Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Bogdan BintuHoward Hughes Medical Institute, Department of Chemistry and Chemical Biology and Department of Physics, Harvard University, Cambridge, MA, USA.
Colin KernCenter for Epigenomics, Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Mattia ConteDipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, Complesso di Monte Sant'Angelo, Naples, Italy.
Yanxiao ZhangLudwig Institute for Cancer Research, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9618-637X
Simona BiancoDipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, Complesso di Monte Sant'Angelo, Naples, Italy.ORCID http://orcid.org/0000-0001-5819-060X
Andrea M ChiarielloDipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, Complesso di Monte Sant'Angelo, Naples, Italy.ORCID http://orcid.org/0000-0002-6112-0167
Miao YuLudwig Institute for Cancer Research, La Jolla, CA, USA.
Rong HuLudwig Institute for Cancer Research, La Jolla, CA, USA.
Melodi TastemelDepartment of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Ivan JuricDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Ming HuDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.ORCID http://orcid.org/0000-0003-0987-2916
Mario NicodemiDipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, Complesso di Monte Sant'Angelo, Naples, Italy.
Xiaowei ZhuangHoward Hughes Medical Institute, Department of Chemistry and Chemical Biology and Department of Physics, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6034-7853
Bing RenLudwig Institute for Cancer Research, La Jolla, CA, USA. biren@health.ucsd.edu.ORCID http://orcid.org/0000-0002-5435-1127
University of California San Diego · USIstituto Nazionale di Fisica Nucleare, Sezione di Napoli · ITLudwig Cancer Research · USCleveland Clinic · USHoward Hughes Medical Institute · USLudwig Cancer Research · BEMax Delbrück Center · DE

Funding

Generation of novel cell type specific mouse genetic toolsU19MH114830 · NIMH · ALLEN INSTITUTE · PI ZENG, HONGKUI · 2017 to 2021
$64.7M
San Diego Center for 4D Nucleome ResearchU54DK107977 · NIDDK · LUDWIG INSTITUTE FOR CANCER RES LTD · PI REN, BING · 2015 to 2019
$9.4M
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
Dissecting the cis-regulatory roles of transposable elements in human cancersK99CA252020 · NCI · LUDWIG INSTITUTE FOR CANCER RES LTD · PI ZHANG, YANXIAO · 2020 to 2021
$227k
Howard Hughes Medical InstituteNCI NIH HHS K99 CA252020NHGRI NIH HHS UM1 HG011585NIDDK NIH HHS U54 DK107977NIMH NIH HHS U19 MH114830
6 · The paper itself

Abstract

Insulators play a critical role in spatiotemporal gene regulation in animals. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here we explore the sequence requirements of CTCF-mediated transcriptional insulation using a sensitive insulator reporter in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF-binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on upstream flanking sequences at its binding sites. CTCF-binding sites at topologically associating domain boundaries are more likely to function as insulators than those outside topologically associating domain boundaries, independently of binding strength. We demonstrate that insulators form local chromatin domain boundaries and weaken enhancer-promoter contacts. Taken together, our results provide genetic, molecular and structural evidence connecting chromatin topology to the action of insulators in the mammalian genome.

Indexed as

Gene Expression RegulationTranscription, GeneticAnimalsBinding SitesCCCTC-Binding FactorChromatinEnhancer Elements, GeneticHumansInsulator ElementsMiceMouse Embryonic Stem CellsPromoter Regions, GeneticProtein BindingCCCTC-Binding FactorChromatinCTCF protein, human

Identifiers

PMID34002095
PMCPMC8853952
OpenAlexW3161556485

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.