The DOI matches its Crossref record; 98 of the 98 references it cites were found in a registry or an index.
The human β‐globin locus control region: A center of attraction
Abstract
The human beta-globin gene locus is the subject of intense study, and over the past two decades a wealth of information has accumulated on how tissue-specific and stage-specific expression of its genes is achieved. The data are extensive and it would be difficult, if not impossible, to formulate a comprehensive model integrating every aspect of what is currently known. In this review, we introduce the fundamental characteristics of globin locus regulation as well as questions on which much of the current research is predicated. We then outline a hypothesis that encompasses more recent results, focusing on the modification of higher-order chromatin structure and recruitment of transcription complexes to the globin locus. The essence of this hypothesis is that the locus control region (LCR) is a genetic entity highly accessible to and capable of recruiting, with great efficiency, chromatin-modifying, coactivator, and transcription complexes. These complexes are used to establish accessible chromatin domains, allowing basal factors to be loaded on to specific globin gene promoters in a developmental stage-specific manner. We conceptually divide this process into four steps: (a) generation of a highly accessible LCR holocomplex; (b) recruitment of transcription and chromatin-modifying complexes to the LCR; (c) establishment of chromatin domains permissive for transcription; (d) transfer of transcription complexes to globin gene promoters.
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“Some enhancers reside in clusters of a handful116 to even hundreds (‘super enhancers’76,117), whereas many are solo.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [116]
Citations
Cites
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Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL
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- 10.1128/MCB.13.5.2776 · DOI
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GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502
GeneHancer: genome-wide integration of enhancers and target genes in GeneCards
Fishilevich, S., Nudel, R., Rappaport, N., Hadar, R., Plaschkes, I., Stein, T. I., Rosen, N., Kohn, A., Twik, M., Safran, M., et al. (2017) · Database · doi:10.1093/database/bax028 · Cited by 1,270
Mammalian Krüppel-Like Factors in Health and Diseases
McConnell, B. B., & Yang, V. W. (2010) · Physiological Reviews · doi:10.1152/physrev.00058.2009 · Cited by 1,041
Towards a comprehensive catalogue of validated and target-linked human enhancers
Gasperini, M., Tome, J. M., & Shendure, J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0209-0 · Cited by 396
Multiplexed Engineering and Analysis of Combinatorial Enhancer Activity in Single Cells
Xie, S., Duan, J., Li, B., Zhou, P., & Hon, G. C. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.03.007 · Cited by 334
“To testwhetherMosaic-seq canmeasure enhancer function after CRISPR perturbation, we focused on the b-globin locus in K562 cells (Figure 2A), where the enhancer HS2 drives expression of HBG1 and HBG2 (HBG1/2) (Levings and Bungert, 2002).”
Method
Metadata
- Authors
- Levings, P. P., & Bungert, J.
- Affiliations
- University of Florida Health (US)
- ORCID
- Bungert, Jörg
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 2002-03-14
- Volume
- 269
- Issue
- 6
- Pages
- 1589-1599
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W1540381414
- Cited by
- 144
- References
- 98
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 5 · 2014: 3 · 2013: 7 · 2012: 4
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK052356, R01DK058209, DK 52356, DK 58209)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- locus control region, globin gene regulation, chromatin accessibility, chromatin-modifying complexes, transcriptional coactivator, transcriptional complex, tissue-specific gene expression, stage-specific gene expression, chromatin domains, promoter loading
- MeSH terms
- Chromatin, Humans, RNA, Messenger, Gene Expression Regulation, Developmental, Locus Control Region
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