ArticleCell2015
CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function.
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Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 558 papers.
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558citing papers in PubMed
49.4field-weighted citation impact, top 1% of its field
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Who cites it
558 citing papers in PubMed, 1,039 citations in OpenAlex.
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- WAVE2 and REST/NRSF Regulate Clustered Gene Expression by Maintaining Heterochromatin Organization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Histone Acetylation Differentially Modulates CTCF-CTCF Loops and Intra-TAD Interactions.Nature communications · 2026Article
- Genome-wide absolute quantification of chromatin looping.Nature structural & molecular biology · 2026Article
- Wiz regulates clustered protocadherin genes by restricting CTCF/cohesin loop extrusion in a genomic-distance biased manner.PLoS genetics · 2026Article
- Distinct and compensatory roles of STAG1 and STAG2 in post-mitotic genome refolding.Nature communications · 2026Article
- Loop extrusion by cohesin plays a role in enhancer-activated gene expression early in differentiation.Nature communications · 2026Article
- Cohesin bridging as a physical principle of enhancer-promoter communication.bioRxiv : the preprint server for biology · 2026Article
- Cohesin extrudes chromatin loop unidirectionally through two modes of mechanisms in human cells.bioRxiv : the preprint server for biology · 2026Article
- A functional overlap between actively transcribed genes and chromatin insulator elements.The EMBO journal · 2026Article
- A comparative analysis of topological domain callers over RNA-associated interactome.BMC bioinformatics · 2026Article
- Impaired cohesin loading disrupts pancreatic differentiation by Polycomb-driven chromatin rewiring and loop collapse.Communications biology · 2026Article
- Enhancing microbial metabolic capacity through high-energy electron beam-induced intense structural variations.Nature communications · 2026Article
- Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm.Nature cell biology · 2026Article
- NIPBL-mediated 3D genome folding translates enhancer priming into gene activation and safeguards lineage fidelity during embryonic transitions.bioRxiv : the preprint server for biology · 2025Article
- Mapping single-cell diploid chromatin fiber architectures using DAF-seq.Nature biotechnology · 2025Article
- Modeling the long-range effect of an inversion downstream of EFNB1 concludes a 43-year molecular diagnostic odyssey for craniofrontonasal syndrome.European journal of human genetics : EJHG · 2025Article
- Disentangling the architectural and non-architectural functions of CTCF and cohesin in gene regulation.Nature genetics · 2025Article
498 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 9 institutions in 2 countries.
Ya GuoCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Quan XuCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Daniele CanzioDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, 701 West 168(th) Street, New York, NY 10032, USA.
Jia ShouCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Jinhuan LiCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
David U GorkinLudwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Inkyung JungLudwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Haiyang WuCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Yanan ZhaiCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Yuanxiao TangCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Yichao LuCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Yonghu WuCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Zhilian JiaCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Wei LiCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China.
Michael Q ZhangDepartment of Molecular and Cell Biology, Center for Systems Biology, University of Texas at Dallas, Richardson, TX 75080, USA; MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and System Biology, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China.
Bing RenLudwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Adrian R KrainerCold Spring Harbor Laboratory, 1 Bungtown Rd, NY 11724, USA.
Tom ManiatisDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, 701 West 168(th) Street, New York, NY 10032, USA. Electronic address: tm2472@cumc.columbia.edu.
Qiang WuCenter for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, Institute of Systems Biomedicine, Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, SJTU, Shanghai 200240, China; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (MOE), Bio-X Center, School of Life Sciences and Biotechnology, SJTU, Shanghai 200240, China. Electronic address: qwu123@gmail.com.
Renji Hospital · CNState Key Laboratory of Oncogene and Related Genes · CNShanghai Cancer Institute · CNColumbia University Irving Medical Center · USLudwig Cancer Research · USCold Spring Harbor Laboratory · USShanghai Jiao Tong University · CNTsinghua University · CNUniversity of California, San Diego · US
Funding
Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI LINGBO ZHANG · 1987 to 2026
$118.9MVIRAL TRANSACTIVATIONP01CA013106 · NCI · COLD SPRING HARBOR LABORATORY · PI Adrian R Krainer · 1985 to 2026
$116.8MUCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4MProtocadherin Gene Expression and FunctionR01NS043915 · NINDS · HARVARD UNIVERSITY · PI MANIATIS, THOMAS P · 2002 to 2011
$6.5MPROTEIN CODING GENES IN THE HUMAN GENOMER01HG001696 · NHGRI · UNIVERSITY OF TEXAS DALLAS · PI ZHANG, MICHAEL Q · 1997 to 2010
$5.1MProtocadherin Gene Expression and FunctionR56NS043915 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MANIATIS, THOMAS P · 2012 to 2012
$553kNCI NIH HHS 3P01-CA013106-41S1NCI NIH HHS P01 CA013106NCI NIH HHS P30 CA045508NHGRI NIH HHS HG001696NHGRI NIH HHS R01 HG001696NIGMS NIH HHS K12 GM068524NINDS NIH HHS R01 NS043915NINDS NIH HHS R56 NS043915
Abstract
CTCF and the associated cohesin complex play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome-conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and β-globin as model genes. Inversion of CBS elements within the Pcdh enhancer reconfigures the topology of chromatin loops between the distal enhancer and target promoters and alters gene-expression patterns. Thus, although enhancers can function in an orientation-independent manner in reporter assays, in the native chromosome context, the orientation of at least some enhancers carrying CBSs can determine both the architecture of topological chromatin domains and enhancer/promoter specificity. These findings reveal how 3D chromosome architecture can be encoded by linear genome sequences.
Indexed as
Genetic TechniquesAnimalsbeta-GlobinsBinding SitesCadherinsCCCTC-Binding FactorCell Cycle ProteinsChromosomal Proteins, Non-HistoneChromosomesClustered Regularly Interspaced Short Palindromic RepeatsCohesinsDNAEnhancer Elements, GeneticGene ExpressionGenome, HumanHumansbeta-GlobinsCadherinsCCCTC-Binding FactorCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsCTCF protein, humanCtcf protein, mouseDNARepressor Proteins
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