Cited by 224Genomics and Chromatin DynamicsHemoglobinopathies and Related DisordersHemoglobin structure and function

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β-globin Gene Switching and DNase I Sensitivity of the Endogenous β-globin Locus in Mice Do Not Require the Locus Control Region

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Bender, M.A, Bulger, Michael, Close, Jennie, Groudine, Mark·2000·Molecular Cell

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Abstract

We have generated mice with a targeted deletion of the beta-globin locus control region (LCR). Mice homozygous for the deletion die early in embryogenesis but can be rescued with a YAC containing the human beta-globin locus. After germline passage, deletion of the LCR leads to a severe reduction in expression of all mouse beta-like globin genes, but no alteration in the developmental specificity of expression. Furthermore, a DNase I-sensitive "open" chromatin conformation of the locus is established and maintained. Thus, the dominant role of the LCR in the native locus is to confer high-level transcription, and elements elsewhere in the locus are sufficient to establish and maintain an open conformation and to confer developmentally regulated globin gene expression.

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Authors: Bender, M. A., Bulger, M., Close, J., & Groudine, M.
Affiliations: University of Washington (US)
Fred Hutch Cancer Center (US)
Corresponding author: Groudine, Mark
ORCID: Bulger, Michael
Close, Jennie
Groudine, Mark
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2000-02
Volume: 5
Issue: 2
Pages: 387-393
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/s1097-2765(00)80433-5
OpenAlex: W1982328581
Cited by: 224
References: 46
Citations by year: 2026: 2 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 7 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 3
FWCI: 9.77
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4915 d)
Locations: Molecular Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (P30 HD28834, DK54071, DK44746)
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: beta-globin locus control region, DNase I sensitivity, open chromatin, globin gene expression, embryonic lethality, developmental gene expression, chromatin conformation
MeSH terms: Animals, Chromatin, Deoxyribonuclease I, Globins, Heterozygote, Humans, Mice, Mutant Strains, Thalassemia, Gene Rearrangement, Sequence Deletion, Chromosomes, Artificial, Yeast, Gene Expression Regulation, Developmental, DNA Footprinting, Locus Control Region, Mice

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β-globin Gene Switching and DNase I Sensitivity of the Endogenous β-globin Locus in Mice Do Not Require the Locus Control Region

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