The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Looping and Interaction between Hypersensitive Sites in the Active β-globin Locus
Open accessAbstract
Eukaryotic transcription can be regulated over tens or even hundreds of kilobases. We show that such long-range gene regulation in vivo involves spatial interactions between transcriptional elements, with intervening chromatin looping out. The spatial organization of a 200 kb region spanning the murine beta-globin locus was analyzed in expressing erythroid and nonexpressing brain tissue. In brain, the globin cluster adopts a seemingly linear conformation. In erythroid cells the hypersensitive sites of the locus control region (LCR), located 40-60 kb away from the active genes, come in close spatial proximity with these genes. The intervening chromatin with inactive globin genes loops out. Moreover, two distant hypersensitive regions participate in these interactions. We propose that clustering of regulatory elements is key to creating and maintaining active chromatin domains and regulating transcription.
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In the citing paper
“3C confirmed that the LCR comes into close contact with active β-globin genes, whilst the intervening inactive genes are looped out [266].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [266]
In the citing paper
“Two papers published in 2002 used different novel biochemical techniques to demonstrate that the β-globin LCR forms chromosomal loops with the active β-globin genes in vivo.”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [266]
In the citing paper
“Enhancer–promoter looping occurred in erythroid cells, in which the β-globin genes are expressed, but not in brain cells, in which they are not [266].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [266]
In the citing paper
“It has been shown that remote enhancers in the mouse β-globin gene domain form a single complex to which the genes that need to be activated are recruited [32].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [32]
In the citing paper
“First, it was shown that active enhancers are often in physical proximity to the promoters they activate, regardless of the genomic distances between these enhancers and promoters [32,33,34].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [32]
In the citing paper
“In erythroid cells expressing globin genes, a large CTCF-CTCF loop encompasses the beta-globin genes and the locus control region (LCR), consistent with the organization of the locus in an insulated neighborhood.”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Tolhuis et al., 2002
In the citing paper
“In fetal brain cells, CTCF binding to one of the beta-globin loop anchor regions is absent and CTCF-CTCF loop formation is not detected (Splinter et al., 2006; Tolhuis et al., 2002), which suggests that tissue-specific CTCF-CTCF loops participate in developmental gene control.”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Tolhuis et al., 2002
In the citing paper
“Central to the mechanism of globin gene switching is the exclusive interaction between the LCR and globin gene promoters at distinct developmental stages (Carter et al., 2002; Palstra et al., 2008; Tolhuis et al., 2002).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Tolhuis et al., 2002
In the citing paper
“In erythroid cells, a powerful distal enhancer called the locus control region (LCR), composed of multiple DNase I hypersensitive sites (HSs), is in physical proximity to the β-globin genes in a developmentally dynamic manner (Carter et al., 2002; Tolhuis et al., 2002).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Tolhuis et al., 2002
Citations
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Self-citationExpression of a β-globin gene is enhanced by remote SV40 DNA sequences
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Self-citationHeterochromatin Effects on the Frequency and Duration of LCR-Mediated Gene Transcription
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Cited by
Sorted by citations
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212
Three-dimensional folding and functional organization principles of the Drosophila genome
Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., & Cavalli, G. (2012) · Cell · doi:10.1016/j.cell.2012.01.010 · Cited by 1,983
A Phase Separation Model for Transcriptional Control
Hnisz, D., Shrinivas, K., Young, R. A., Chakraborty, A. K., & Sharp, P. A. (2017) · Cell · doi:10.1016/j.cell.2017.02.007 · Cited by 1,753
CTCF: Master Weaver of the Genome
Phillips‐Cremins, J. E., & Corces, V. G. (2009) · Cell · doi:10.1016/j.cell.2009.06.001 · Cited by 1,585
The long-range interaction landscape of gene promoters
Sanyal, A., Lajoie, B. R., Jain, G., & Dekker, J. (2012) · Nature · doi:10.1038/nature11279 · Cited by 1,489
Metadata
- Authors
- Tolhuis, B., Palstra, R.-J., Splinter, E., Grosveld, F., & de Laat, W.
- Affiliations
- Erasmus University Rotterdam (NL)
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2002-12
- Volume
- 10
- Issue
- 6
- Pages
- 1453-1465
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2089894746
- Cited by
- 1,344
- References
- 48
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 39 · 2023: 26 · 2022: 38 · 2021: 44 · 2020: 46 · 2019: 55 · 2018: 58 · 2017: 58 · 2016: 70 · 2015: 68 · 2014: 76 · 2013: 62 · 2012: 84
- FWCI
- 15.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- 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 (clinical) › Hemoglobinopathies and Related Disorders
- Keywords
- chromatin looping, long-range gene regulation, beta-globin locus control region, hypersensitive sites, chromatin domains, erythroid cells, brain tissue, transcriptional regulation
- MeSH terms
- Animals, Binding Sites, Brain, Chromatin, Chromosome Mapping, DNA, Multigene Family, Globins, Liver, Nucleic Acid Conformation, Locus Control Region, Mice
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