Cited by 657Hemoglobinopathies and Related DisordersGenomics and Chromatin DynamicsGenetic Associations and Epidemiology

An Erythroid Enhancer of BCL11A Subject to Genetic Variation Determines Fetal Hemoglobin Level

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Bauer, Daniel E., Kamran, Sophia C., Lessard, Samuel, Xu, Jian, Fujiwara, Yuko, Lin, Carrie, Shao, Zhen, Canver, Matthew C. +10 more·2013·Science

Abstract

BCL11A Variants: Recent chromatin mapping data have suggested that trait-associated variants often mark regulatory DNA. However, there has been little rigorous experimental investigation of regulatory variation. Bauer et al. (p. 253 ; see the Perspective by Hardison and Blobel ) performed an in-depth study of the BCL11A fetal hemoglobin-associated locus. The trait-associated variants revealed a chromatin signature that enhanced erythroid development. The enhancer was required for erythroid expression of BCL11A and thus for globin gene expression.

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Crossref · 10.1126/science.1242088

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  • The BCL11A erythroid-specific enhancer consists of 3 DNase hypersensitive sites 162, 158, and 155 kb from the transcription initiation site.

    “This enhancer consists of 3 DNase hypersensitive sites 162, 158, and 155 kb from the transcription initiation site.19”

    From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [19]

    The passage on DNase I hypersensitivity reports three erythroid sites in BCL11A intron 2, supporting the claim's site count. But it places them at +62, +58 and +55 kb from the transcription start site, not 162, 158 and 155 kb. (LLM, conf=0.90)

    Experimental — accuracy not yet measured
  • Genomewide association studies found SNPs associated with higher fetal hemoglobin in adults.

    “Genomewide association studies have identified single-nucleotide polymorphisms (SNPs) associated with increased expression of fetal hemoglobin in adults.26”
  • Functional variants of BCL11A are marked by single nucleotide polymorphisms in intron 2 that tag an erythroid-specific enhancer.

    “Functional variants of BCL11A are marked by single nucleotide polymorphisms (SNPs) in intron 2 that tag an erythroid-specific enhancer.19”

    From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [19]

  • The sentinel SNP marking the BCL11A QTL is rs1427407.

    “The sentinel SNP marking this QTL is rs1427407.”

    From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [19]

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Authors
Bauer, D. E., Kamran, S. C., Lessard, S., Xu, J., Fujiwara, Y., Lin, C., Shao, Z., Canver, M. C., Smith, E. C., Pinello, L., Sabo, P. J., Vierstra, J., Voit, R. A., Yuan, G.-C., Porteus, M. H., Stamatoyannopoulos, J. A., Lettre, G., & Orkin, S. H.
Affiliations
  • Boston Children's Hospital (US)
  • Howard Hughes Medical Institute (US)
  • Montreal Heart Institute (CA)
  • Harvard University (US)
  • Dana-Farber Cancer Institute (US)
  • University of Washington (US)
  • Stanford University (US)
Corresponding author
Orkin, Stuart H.
Venue
Science
Published
2013-10-11
Volume
342
Issue
6155
Pages
253-257
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2008989169
Cited by
653
References
54
Citations by year
2026: 42 · 2025: 50 · 2024: 64 · 2023: 42 · 2022: 47 · 2021: 48 · 2020: 45 · 2019: 38 · 2018: 49 · 2017: 48 · 2016: 80 · 2015: 59 · 2014: 37 · 2013: 4
FWCI
29.32
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • Canadian Institutes of Health Research (123382)
  • National Heart, Lung, and Blood Institute (P01HL032262, R01HL032259)
  • National Human Genome Research Institute (U54HG007010, U54HG004594, R01HG005085)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK049216, K08DK093705)
Topics
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
BCL11A, fetal hemoglobin, common genetic variants, transcription factor binding, fine mapping, erythroid cells, B cells, β-hemoglobinopathies, genome editing
MeSH terms
Animals, Carrier Proteins, Cells, Cultured, Chromatin, Chromosome Mapping, Enhancer Elements, Genetic, Fetal Hemoglobin, Gene Expression Regulation, Genetic Engineering, Hemoglobinopathies, Humans, Nuclear Proteins, Repressor Proteins, Transcription Factors, Genetic Variation, Gene Targeting, Erythroid Cells, Cell Line, Tumor, Chromatin Immunoprecipitation, Mice, Precursor Cells, B-Lymphoid, Genome-Wide Association Study

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