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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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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