Spatial configuration of the chicken α-globin gene domain: immature and active chromatin hubs
Open accessAbstract
The spatial configuration of the chicken alpha-globin gene domain in erythroid and lymphoid cells was studied by using the Chromosome Conformation Capture (3C) approach. Real-time PCR with TaqMan probes was employed to estimate the frequencies of cross-linking of different restriction fragments within the domain. In differentiated cultured erythroblasts and in 10-day chick embryo erythrocytes expressing 'adult' alpha(A) and alpha(D) globin genes the following elements of the domain were found to form an 'active' chromatin hub: upstream Major Regulatory Element (MRE), -9 kb upstream DNase I hypersensitive site (DHS), -4 kb upstream CpG island, alpha(D) gene promoter and the downstream enhancer. The alpha(A) gene promoter was not present in the 'active' chromatin hub although the level of alpha(A) gene transcription exceeded that of the alpha(D) gene. Formation of the 'active' chromatin hub was preceded by the assembly of multiple incomplete hubs containing MRE in combination with either -9 kb DHS or other regulatory elements of the domain. These incomplete chromatin hubs were present in proliferating cultured erythroblasts which did not express globin genes. In lymphoid cells only the interaction between the alpha(D) promoter and the CpG island was detected.
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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 [487]
The Discussion (page not provided) reports that the active αA promoter showed little association with upstream regulatory elements, supporting the possibility of promoter activity without direct contact with each element. It does not propose an enhancer chain or say that a signal passes along one. (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 [487]
The Results (page not available in our copy) report a clear interaction between the LCR-like MRE and a downstream enhancer. The Discussion describes a chromatin hub involving multiple regulatory elements, but does not establish an enhancer-only chain or network; that part of the claim goes beyond the paper's evidence. (LLM, conf=0.82)
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Chromosome conformation capture (from 3C to 5C) and its ChIP-based modification
Gavrilov, A., Eivazova, E., Pirozhkova, I., Lipinski, M., Razin, S., & Vassetzky, Y. (2009) · Methods in molecular biology · doi:10.1007/978-1-60327-414-2_12 · Cited by 82 · 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
- Authors
- Gavrilov, A. A., & Razin, S. V.
- Affiliations
- Russian Academy of Sciences (RU)
- Corresponding author
- Razin, Sergey V.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-07-11
- Volume
- 36
- Issue
- 14
- Pages
- 4629-4640
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC2504291
- OpenAlex
- W2088249929
- Cited by
- 48
- References
- 2
- Citations by year
- 2022: 1 · 2021: 3 · 2020: 3 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 2 · 2013: 4 · 2012: 6
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Russian Foundation for Basic Research
- Russian Academy of Sciences (08-04)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- 3D genome organization, erythroblasts, lymphoid cells, DNase I hypersensitive sites, CpG islands, enhancers, globin gene transcription, erythroid differentiation
- MeSH terms
- Animals, Bacterial Proteins, Cell Differentiation, Cell Line, Cell Line, Transformed, Chick Embryo, Chickens, Chromatin, Enhancer Elements, Genetic, Erythroblasts, Erythrocytes, Globins, Lymphocytes, Models, Genetic, Promoter Regions, Genetic, Transcription, Genetic, Restriction Mapping, Deoxyribonuclease BamHI, Deoxyribonucleases, Type II Site-Specific, Polymerase Chain Reaction, CpG Islands, Locus Control Region, Regulatory Elements, Transcriptional
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