Multiple interactions between regulatory regions are required to stabilize an active chromatin hub
Open accessAbstract
The human β-globin locus control region (LCR) is required for the maintenance of an open chromatin configuration of the locus. It interacts with the genes and the hypersensitive regions flanking the locus to form an active chromatin hub (ACH) transcribing the genes. Proper developmental control of globin genes is largely determined by gene proximal regulatory sequences. Here, we provide the first functional evidence of the role of the most active sites of the LCR and the promoter of the β-globin gene in the maintenance of the ACH. When the human β-globin gene promoter is deleted in the context of a full LCR, the ACH is maintained with the β-globin gene remaining in proximity. Additional deletion of hypersensitive site HS3 or HS2 of the LCR shows that HS3, but not HS2, in combination with the β-globin promoter is crucial for the maintenance of the ACH at the definitive stage. We conclude that multiple interactions between the LCR and the β-globin gene are required to maintain the appropriate spatial configuration in vivo.
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In an enhancer chain, not all enhancers need to contact the gene promoter directly; the signal could be passed along the chain.
“In this mechanism, not all of the enhancers need to contact the gene promoter directly; rather, the signal could be passed along the chain.”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [486]
In 'Deletion of the β-globin promoter combined with LCR HS2 and HS3 deletion' (page unavailable), the paper suggests that HS3 interacts with sequences other than the β-globin promoter and that this interaction matters for transcription. This supports the possibility that a regulatory element need not contact the promoter directly, but the paper does not describe a signal being passed along an enhancer chain. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThere is evidence for enhancer-enhancer interactions that create an enhancer chain or network.
“there is also evidence for enhancer–enhancer interactions that create an enhancer “chain” or network [486–489].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [486]
The Discussion describes a chromatin hub formed by interactions among regulatory hypersensitive sites, supporting the network aspect of the claim. But the paper says it remains unclear whether individual sites in the locus control region interact with one another or instead interact simultaneously with a gene; it does not establish an enhancer–enhancer chain. Our copy provides section labels but no page numbers. (LLM, conf=0.82)
Experimental — accuracy not yet measuredActivation of a gene or gene locus by multiple enhancers is quite common.
“Although the number of enhancers in mammalian genomes can be overestimated, activation of a gene or gene locus by multiple enhancers is quite common [26].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [26]
The introductory passage describes several regulatory sites forming an active chromatin hub that interacts with genes in the human β-globin locus. This supports the existence of a locus regulated by multiple elements, but the paper does not establish that activation by multiple enhancers is common across genes or loci. (LLM, conf=0.83)
Experimental — accuracy not yet measured
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Cites
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The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation
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Enhancer Function in the 3D Genome
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- Authors
- Patrinos, G. P., de Krom, M., de Boer, E., Langeveld, A., Imam, A. M. A., Strouboulis, J., de Laat, W., & Grosveld, F. G.
- Affiliations
- Erasmus MC (NL)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-06-15
- Volume
- 18
- Issue
- 12
- Pages
- 1495-1509
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC423198
- OpenAlex
- W2148212953
- Cited by
- 170
- References
- 6
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 3 · 2013: 9 · 2012: 7
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Funders
- European Commission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- beta-globin locus control region, beta-globin promoter, chromatin interactions, open chromatin, globin gene regulation, developmental gene regulation
- MeSH terms
- Animals, Chromatin, Globins, Humans, Mice, Transgenic, Nucleic Acid Conformation, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Sequence Deletion, Locus Control Region, Mice
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