Binding patterns of BCL11A in the globin and GATA1 loci and characterization of the BCL11A fetal hemoglobin locus
Abstract
BCL11A is a major regulator of fetal hemoglobin production. Reduced levels of BCL11A have been shown to delay switching from fetal to adult hemoglobin, suggesting that it acts as a stage-specific repressor of gamma globin expression. We have carried out a survey of BCL11A binding in the globin, BCL11A and GATA1 loci by ChIP-on-chip analysis in primary human erythroid cells. We found strong occupancy in both alpha and beta globin upstream regulatory regions as well as in regions involved in switching and hereditary persistence of fetal hemoglobin. Genetic studies have identified a restricted 14kb region in BCL11A intron 2 as being highly associated with HbF levels. Strong GATA-1 binding and acetylated histone H3 was found in this area, which could be indicative of a regulatory element, changes in which might be responsible for the overall regulation of BCL11A. We also observed BCL11A and GATA-1 binding in a known auto-regulatory promoter element of the GATA1 locus.
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BCL11A is a bona fide repressor of HbF expression.
“Subsequent studies demonstrated that BCL11A, a zinc- fi nger transcription factor, is a bona fi de repressor of HbF expression (4 -7).”
From Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A (2013) · cites this paper as [7]
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Direct promoter repression by BCL11A controls the fetal to adult hemoglobin switch
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- Authors
- Jawaid, K., Wahlberg, K., Thein, S. L., & Best, S.
- Affiliations
- King's College London (GB)
- Corresponding author
- Thein, Swee Lay
- Venue
- Blood Cells, Molecules, and Diseases
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 45
- Issue
- 2
- Pages
- 140-146
- ISSN
- 1079-9796 (ISSN-L)
- OpenAlex
- W2070876549
- Cited by
- 64
- References
- 4
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 8 · 2017: 9 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 4
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood Cells Molecules and Diseases (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- BCL11A, fetal hemoglobin, globin gene regulation, GATA-1, beta-globin promoter, hereditary persistence of fetal hemoglobin, hemoglobin switching, histone H3 acetylation, erythroid cells, transcriptional repressor
- MeSH terms
- Carrier Proteins, Fetal Hemoglobin, Gene Expression Regulation, Hemoglobinopathies, Histones, Humans, Nuclear Proteins, Repressor Proteins, K562 Cells, Erythroid Cells, Regulatory Elements, Transcriptional, GATA1 Transcription Factor, Genetic Loci
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