Cited by 144Genomics and Chromatin DynamicsHemoglobinopathies and Related DisordersHemoglobin structure and function

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The human β‐globin locus control region: A center of attraction

Levings, Padraic P., Bungert, Jörg·2002·European Journal of Biochemistry

DOI 10.1046/j.1432-1327.2002.02797.x

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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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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
DOI: 10.1046/j.1432-1327.2002.02797.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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The human β‐globin locus control region: A center of attraction

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