Cited by 205Genomics and Chromatin DynamicsChromatin Remodeling and CancerEpigenetics and DNA Methylation

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CTCF-dependent enhancer-blocking by alternative chromatin loop formation

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Hou, Chunhui, Zhao, Hui, Tanimoto, Keiji, Dean, Ann·2008·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0808506106PMC PMC2629272

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Abstract

The mechanism underlying enhancer-blocking by insulators is unclear. We explored the activity of human beta-globin HS5, the orthologue of the CTCF-dependent chicken HS4 insulator. An extra copy of HS5 placed between the beta-globin locus control region (LCR) and downstream genes on a transgene fulfills the classic predictions for an enhancer-blocker. Ectopic HS5 does not perturb the LCR but blocks gene activation by interfering with RNA pol II, activator and coactivator recruitment, and epigenetic modification at the downstream beta-globin gene. Underlying these effects, ectopic HS5 disrupts chromatin loop formation between beta-globin and the LCR, and instead forms a new loop with endogenous HS5 that topologically isolates the LCR. Both enhancer-blocking and insulator-loop formation depend on an intact CTCF site in ectopic HS5 and are sensitive to knock-down of the CTCF protein by siRNA. Thus, intrinsic looping activity of CTCF sites can nullify LCR function.

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Dekker, J., Rippe, K., Dekker, M., & Kleckner, N. (2002) · Science · doi:10.1126/science.1067799 · Cited by 3,652
Looping and Interaction between Hypersensitive Sites in the Active β-globin Locus
Tolhuis, B., Palstra, R.-J., Splinter, E., Grosveld, F., & de Laat, W. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00781-5 · Cited by 1,344
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Wendt, K. S., Yoshida, K., Itoh, T., Bando, M., Koch, B., Schirghuber, E., Tsutsumi, S., Nagae, G., Ishihara, K., Mishiro, T., et al. (2008) · Nature · doi:10.1038/nature06634 · Cited by 1,193
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Bell, A. C., West, A. G., & Felsenfeld, G. (1999) · Cell · doi:10.1016/s0092-8674(00)81967-4 · Cited by 1,101
Analysis of the Vertebrate Insulator Protein CTCF-Binding Sites in the Human Genome
Kim, T. H., Abdullaev, Z., Smith, A. D., Ching, K. A., Loukinov, D. I., Green, R. D., Zhang, M. Q., Lobanenkov, V. V., & Ren, B. (2007) · Cell · doi:10.1016/j.cell.2006.12.048 · Cited by 1,022
Cohesins Functionally Associate with CTCF on Mammalian Chromosome Arms
Parelho, V., Hadjur, S., Spivakov, M., Leleu, M., Sauer, S., Gregson, H. C., Jarmuz, A., Canzonetta, C., Webster, Z., Nesterova, T., et al. (2008) · Cell · doi:10.1016/j.cell.2008.01.011 · Cited by 900
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Farrell, C. M., Grinberg, A., Huang, S. P., Chen, D., Pichel, J. G., Westphal, H., & Felsenfeld, G. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.26.14554 · Cited by 36
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A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
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Formation of chromosomal domains by loop extrusion
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CTCF: Master Weaver of the Genome
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“, 2008), and placing an enhancer and promoter on separate loops can isolate the enhancer to render it inactive (Ameres et al., 2005; Hou et al., 2008).”
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Authors: Hou, C., Zhao, H., Tanimoto, K., & Dean, A.
Affiliations: National Institutes of Health (US)
University of Tsukuba (JP)
Corresponding author: Dean, Ann
ORCID: Hou, Chunhui
Zhao, Hui
Tanimoto, Keiji
Dean, Ann
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2008-12-23
Volume: 105
Issue: 51
Pages: 20398-20403
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0808506106
PMC: PMC2629272
OpenAlex: W2069172573
Cited by: 205
References: 44
Citations by year: 2026: 7 · 2025: 1 · 2024: 4 · 2023: 9 · 2022: 13 · 2021: 13 · 2020: 17 · 2019: 12 · 2018: 21 · 2017: 9 · 2016: 13 · 2015: 9 · 2014: 9 · 2013: 13 · 2012: 15
FWCI: 5.48
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Japan Society for the Promotion of Science (20678002)
National Institute of Diabetes and Digestive and Kidney Diseases
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords: CTCF, enhancer blocking, insulators, chromatin looping, locus control region, beta-globin, RNA polymerase II recruitment, coactivator recruitment, epigenetic modifications, topologically associating domains, chromatin topology
MeSH terms: CCCTC-Binding Factor, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Humans, Repressor Proteins, Transgenes, Locus Control Region, Insulator Elements, Epigenesis, Genetic, beta-Globins

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CTCF-dependent enhancer-blocking by alternative chromatin loop formation

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