The mouse alpha-globin cluster: a paradigm for studying genome regulation and organization
Open accessAbstract
The mammalian globin gene clusters provide a paradigm for studying the relationship between genome structure and function. As blood stem cells undergo lineage specification and differentiation to form red blood cells, the chromatin structure and expression of the α-globin cluster change. The gradual activation of the α-globin genes in well-defined cell populations has enabled investigation of the structural and functional roles of its enhancers, promoters and boundary elements. Recent studies of gene regulatory processes involving these elements at the mouse α-globin cluster have brought new insights into the general principles underlying the three-dimensional structure of the genome and its relationship to gene expression throughout time.
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The α-SE is activated exclusively during terminal erythroid differentiation, meaning its manipulation has no effect on cell fate or in non-erythroid cells.
“and the SE is activated exclusively during terminal erythroid differentiation, meaning its manipulation has no effect on cell fate or in non-erythroid cells.”
From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [58]
The Introduction (page unavailable) says perturbing α-globin regulatory elements can leave cell lineage, differentiation, and maturation unchanged. But the section on α-globin activation during erythropoiesis says the enhancers become accessible in very early erythroid progenitors, not exclusively during terminal differentiation. The paper does not establish that manipulating them has no effect in non-erythroid cells. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe α-SE and the TAD in which it is contained have been extensively characterized.
“The α-SE is an ideal genetic model for this study; the SE and the TAD in which it is contained have been extensively characterized,58”
From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [58]
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BackgroundResultSelf-citationMultiplexed analysis of chromosome conformation at vastly improved sensitivity
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Super-enhancers include classical enhancers and facilitators to fully activate gene expression
Blayney, J. W., Francis, H., Rampasekova, A., Camellato, B., Mitchell, L., Stolper, R., Cornell, L., Babbs, C., Boeke, J. D., Higgs, D. R., et al. (2023) · Cell · doi:10.1016/j.cell.2023.11.030 · Cited by 196 · see citing works
Self-citation
- Authors
- Oudelaar, A. M., Beagrie, R. A., Kassouf, M. T., & Higgs, D. R.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- University of Oxford (GB)
- Corresponding author
- Oudelaar, A Marieke
- Higgs, Douglas R
- Venue
- Current Opinion in Genetics & Development
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 67
- Pages
- 18-24
- ISSN
- 0959-437X (ISSN-L)
- PMC
- PMC8100094
- OpenAlex
- W3100505464
- Cited by
- 27
- References
- 12
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 3
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Genetics & Development (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Wellcome Trust
- Medical Research Council
- 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 › Cell Biology › Hemoglobin structure and function
- Keywords
- alpha-globin gene cluster, globin gene regulation, enhancers, promoter, 3D genome organization, blood stem cells, erythroid differentiation, gene expression, mice
- MeSH terms
- Animals, Chromatin, Gene Expression Regulation, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Genome, Mice, alpha-Globins
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