Structural and functional conservation at the boundaries of the chicken β‐globin domain
Open accessAbstract
We show that the 3' boundary of the chicken beta-globin locus bears striking structural similarities to the 5' boundary. In erythroid cells a clear transition in DNase I sensitivity of chromatin at the 3' end of the locus is observed, the location of this transition is marked by a constitutive DNase I hypersensitive site (HS), and DNA spanning this site has the enhancer-blocking capacity of an insulator. This HS contains a binding site for the transcription factor CTCF. As in the case of the 5' insulator, the CTCF site is both necessary and sufficient for the enhancer-blocking activity of the 3' boundary. The position of this insulator is consistent with our proposal that it may function to maintain the distinct regulatory programs of the globin genes and their closely appended 3' neighbor, an odorant receptor gene. We conclude that both boundaries of the chicken beta-globin domain are capable of playing functionally similar roles and that the same protein is a necessary component of the molecular mechanism through which these boundaries are defined.
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CTCF binding has an insulating capacity, effectively blocking signals between enhancers and their target genes in the β-globin and H19/Igf2 loci.
“More unusually, it emerged that CTCF binding has an insulating capacity, effectively blocking signals between enhancers and their target genes in the β-globin and H19/Igf2 loci [323–326].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [324]
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CTCF mediates long-range chromatin looping and local histone modification in the β-globin locus
Splinter, E., Heath, H., Kooren, J., Palstra, R.-J., Klous, P., Grosveld, F., Galjart, N., & de Laat, W. (2006) · Genes & Development · doi:10.1101/gad.399506 · Cited by 677 · see citing works
CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease
Ohlsson, R., Renkawitz, R., & Lobanenkov, V. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02366-6 · Cited by 591 · see citing works
Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain
Forsberg, E. C., Downs, K. M., Christensen, H. M., Im, H., Nuzzi, P. A., & Bresnick, E. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.26.14494 · Cited by 226 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
Anguita, E., Johnson, C. A., Wood, W. G., Turner, B. M., & Higgs, D. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201413098 · Cited by 70 · see citing works
Bender, M. A., Byron, R., Ragoczy, T., Telling, A., Bulger, M., & Groudine, M. (2006) · Blood · doi:10.1182/blood-2006-04-014431 · Cited by 59 · see citing works
- Authors
- Saitoh, N., Bell, A. C., Recillas‐Targa, F., West, A. G., Simpson, M., Pikaart, M., & Felsenfeld, G.
- Affiliations
- National Institutes of Health (US)
- Hope College (US)
- Corresponding author
- Felsenfeld, Gary
- Venue
- The EMBO Journal
- Published
- 2000-05-15
- Volume
- 19
- Issue
- 10
- Pages
- 2315-2322
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC384375
- OpenAlex
- W2159284172
- Cited by
- 149
- References
- 2
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2013: 2 · 2012: 7
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science
- 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
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- insulators, CTCF binding sites, DNase I hypersensitive sites, enhancer blocking, DNase I sensitivity, globin gene regulation, erythroid cells, chromatin structure
- MeSH terms
- CCCTC-Binding Factor, Animals, Binding Sites, Chickens, Chromatin, Deoxyribonuclease I, DNA-Binding Proteins, Globins, Repressor Proteins, Substrate Specificity, Transcription Factors
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