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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
Open accessAbstract
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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“previous studies deleting the entire β-globin SE showed that the β-globin genes remain accessible and marked by histone acetylation;55–57”
From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [55]
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“These models were initially applied to the mammalian β-globin locus, in which the developmental β-globin genes are regulated by a powerful tissue-specific enhancer known as a locus control region (LCR) [254–257].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [256]
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“The strong induction of b-globin transcription by ZF-Ldb1 or ZFSA implicates an involvement of the LCR and, hence, chromatin looping, because in the absence of the LCR, b-globin transcription is very low (Bender et al., 2000).”
InfluentialLong-range chromatin regulatory interactions in vivo
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Metadata
- Authors
- Bender, M. A., Bulger, M., Close, J., & Groudine, M.
- Affiliations
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Groudine, Mark
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 5
- Issue
- 2
- Pages
- 387-393
- ISSN
- 1097-2765 (ISSN-L)
- 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
- 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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