The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
An Erythroid Enhancer of BCL11A Subject to Genetic Variation Determines Fetal Hemoglobin Level
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Genomewide association studies have identified single-nucleotide polymorphisms (SNPs) associated with increased expression of fetal hemoglobin in adults.26”
From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [26]
The cited source says what the claim attributes to it.
In the citing paper
“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 cited source says what the claim attributes to it.
In the citing paper
“The sentinel SNP marking this QTL is rs1427407.”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [19]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA
Maurano, M. T., Humbert, R., Rynes, E., Thurman, R. E., Haugen, E., Wang, H., Reynolds, A. P., Sandstrom, R., Qu, H., Brody, J., et al. (2012) · Science · doi:10.1126/science.1222794 · Cited by 3,716
Self-citationMapping and analysis of chromatin state dynamics in nine human cell types
Ernst, J., Kheradpour, P., Mikkelsen, T. S., Shoresh, N., Ward, L. D., Epstein, C. B., Zhang, X., Wang, L., Issner, R., Coyne, M., et al. (2011) · Nature · doi:10.1038/nature09906 · Cited by 2,898
The accessible chromatin landscape of the human genome
Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., et al. (2012) · Nature · doi:10.1038/nature11232 · Cited by 2,679
Self-citationRare-Variant Association Testing for Sequencing Data with the Sequence Kernel Association Test
Wu, M. C., Lee, S., Cai, T., Li, Y., Boehnke, M., & Lin, X. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.05.029 · Cited by 2,373
Genome editing with engineered zinc finger nucleases
Urnov, F. D., Rebar, E. J., Holmes, M. C., Zhang, H. S., & Gregory, P. D. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2842 · Cited by 2,285
A TALE nuclease architecture for efficient genome editing
Miller, J. C., Tan, S., Qiao, G., Barlow, K. A., Wang, J., Xia, D. F., Meng, X., Paschon, D. E., Leung, E., Hinkley, S. J., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1755 · Cited by 2,098
Čermák, T., Doyle, E., Christian, M. L., Wang, L., Zhang, Y., Schmidt, C. L., Baller, J. A., Somia, N. V., Bogdanove, A. J., & Voytas, D. F. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr218 · Cited by 2,034
TALENs: A widely applicable technology for targeted genome editing
Joung, J. K., & Sander, J. D. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3486 · Cited by 1,650
Human genetic variation and its contribution to complex traits
Frazer, K. A., Murray, S. S., Schork, N. J., & Topol, E. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2554 · Cited by 1,073
Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A
Sankaran, V. G., Menne, T. F., Xu, J., Akie, T. E., Lettre, G., Van Handel, B., Mikkola, H. K. A., Hirschhorn, J. N., Cantor, A. B., & Orkin, S. H. (2008) · Science · doi:10.1126/science.1165409 · Cited by 919
Self-citationMelnikov, A., Murugan, A., Zhang, X., Tesileanu, T., Wang, L., Rogov, P., Feizi, S., Gnirke, A., Callan, C. G., Kinney, J. B., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2137 · Cited by 711
Uda, M., Galanello, R., Sanna, S., Lettre, G., Sankaran, V. G., Chen, W., Usala, G., Busonero, F., Maschio, A., Albai, G., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711566105 · Cited by 672
Self-citationLettre, G., Sankaran, V. G., Bezerra, M., Araujo, A. S., Uda, M., Sanna, S., Cao, A., Schlessinger, D., Costa, F. F., Hirschhorn, J. N., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804799105 · Cited by 577
Self-citationMassively parallel functional dissection of mammalian enhancers in vivo
Patwardhan, R. P., Hiatt, J. B., Witten, D. M., Kim, M. J., Smith, R. P., May, D., Lee, C., Andrie, J. M., Lee, S.-I., Cooper, G. M., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2136 · Cited by 536
A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15
Menzel, S., Garner, C., Gut, I., Matsuda, F., Yamaguchi, M., Heath, S., Foglio, M., Zelenika, D., Boland, A., Rooks, H., et al. (2007) · Nature Genetics · doi:10.1038/ng2108 · Cited by 529
ATM stabilizes DNA double-strand-break complexes during V(D)J recombination
Bredemeyer, A. L., Sharma, G. G., Huang, C., Helmink, B. A., Walker, L. M., Khor, K. C., Nuskey, B., Sullivan, K. E., Pandita, T. K., Bassing, C. H., et al. (2006) · Nature · doi:10.1038/nature04866 · Cited by 435
Developmental and species-divergent globin switching are driven by BCL11A
Sankaran, V. G., Xu, J., Ragoczy, T., Ippolito, G. C., Walkley, C. R., Maika, S. D., Fujiwara, Y., Ito, M., Groudine, M., Bender, M. A., et al. (2009) · Nature · doi:10.1038/nature08243 · Cited by 379
Self-citationXu, J., Sankaran, V. G., Ni, M., Menne, T. F., Puram, R. V., Kim, W., & Orkin, S. H. (2010) · Genes & Development · doi:10.1101/gad.1897310 · Cited by 361
Self-citationHe, A., Kong, S. W., Ma, Q., & Pu, W. T. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016959108 · Cited by 360
Bcl11a is essential for normal lymphoid development
Liu, P., Keller, J. R., Ortiz, M., Tessarollo, L., Rachel, R. A., Nakamura, T., Jenkins, N. A., & Copeland, N. G. (2003) · Nature Immunology · doi:10.1038/ni925 · Cited by 351
Correction of Sickle Cell Disease in Adult Mice by Interference with Fetal Hemoglobin Silencing
Xu, J., Peng, C., Sankaran, V. G., Shao, Z., Esrick, E. B., Chong, B. G., Ippolito, G. C., Fujiwara, Y., Ebert, B. L., Tucker, P. W., et al. (2011) · Science · doi:10.1126/science.1211053 · Cited by 326
Self-citationSeventy-five genetic loci influencing the human red blood cell
van der Harst, P., Zhang, W., Leach, I. M., Rendon, A., Verweij, N., Sehmi, J., Paul, D. S., Elling, U., Allayee, H., Li, X., et al. (2012) · Nature · doi:10.1038/nature11677 · Cited by 306
Galarneau, G., Palmer, C. D., Sankaran, V. G., Orkin, S. H., Hirschhorn, J. N., & Lettre, G. (2010) · Nature Genetics · doi:10.1038/ng.707 · Cited by 273
Self-citationIntragenic Enhancers Act as Alternative Promoters
Kowalczyk, M. S., Hughes, J. R., Garrick, D., Lynch, M. D., Sharpe, J. A., Sloane-Stanley, J. A., McGowan, S. J., De Gobbi, M., Hosseini, M., Vernimmen, D., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.12.021 · Cited by 267
Targeted chromosomal deletions in human cells using zinc finger nucleasesPreprint
Lee, H. J., Kim, E., & Kim, J. (2009) · Genome Research · doi:10.1101/gr.099747.109 · Cited by 259
The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation
Soler, E., Andrieu-Soler, C., de Boer, E., Bryne, J. C., Thongjuea, S., Stadhouders, R., Palstra, R.-J., Stevens, M., Kockx, C., van IJcken, W., et al. (2010) · Genes & Development · doi:10.1101/gad.551810 · Cited by 245
Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A
Xu, J., Bauer, D. E., Kerenyi, M. A., Vo, T. D., Hou, S., Hsu, Y.-J., Yao, H., Trowbridge, J. J., Mandel, G., & Orkin, S. H. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303976110 · Cited by 233
Self-citationBcl11a is essential for lymphoid development and negatively regulates p53
Yu, Y., Wang, J., Khaled, W. T., Burke, S., Li, P., Chen, X., Yang, W., Jenkins, N. A., Copeland, N. G., Zhang, S., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20121846 · Cited by 223
Xu, J., Shao, Z., Glass, K., Bauer, D. E., Pinello, L., Handel, B. V., Hou, S., Stamatoyannopoulos, J. A., Mikkola, H. K. A., Yuan, G., et al. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.09.003 · Cited by 207
Self-citationA complex task? Direct modulation of transcription factors with small molecules
Koehler, A. N. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2010.03.022 · Cited by 189
Nuinoon, M., Makarasara, W., Mushiroda, T., Setianingsih, I., Wahidiyat, P. A., Sripichai, O., Kumasaka, N., Takahashi, A., Svasti, S., Munkongdee, T., et al. (2009) · Human Genetics · doi:10.1007/s00439-009-0770-2 · Cited by 186
Kassouf, M. T., Hughes, J. R., Taylor, S., McGowan, S. J., Soneji, S., Green, A. L., Vyas, P., & Porcher, C. (2010) · Genome Research · doi:10.1101/gr.104935.110 · Cited by 185
Reawakening fetal hemoglobin: prospects for new therapies for the β-globin disorders
Bauer, D. E., Kamran, S. C., & Orkin, S. H. (2012) · Blood · doi:10.1182/blood-2012-06-292078 · Cited by 177
Self-citationCTIP1 and CTIP2 are differentially expressed during mouse embryogenesis
Leid, M., Ishmael, J. E., Avram, D., Shepherd, D., Fraulob, V., & Dollé, P. (2004) · Gene Expression Patterns · doi:10.1016/j.modgep.2004.03.009 · Cited by 156
McGrath, K. E., Frame, J. M., Fromm, G. J., Koniski, A. D., Kingsley, P. D., Little, J. A., Bulger, M., & Palis, J. (2011) · Blood · doi:10.1182/blood-2010-12-325357 · Cited by 144
Solovieff, N., Milton, J. N., Hartley, S. W., Sherva, R., Sebastiani, P., Dworkis, D. A., Klings, E. S., Farrer, L. A., Garrett, M. E., Ashley‐Koch, A. E., et al. (2009) · Blood · doi:10.1182/blood-2009-08-239517 · Cited by 144
Amelioration of Sardinian 0 thalassemia by genetic modifiers
Galanello, R., Sanna, S., Perseu, L., Sollaino, M. C., Satta, S., Lai, M. E., Barella, S., Uda, M., Usala, G., Abecasis, G. R., et al. (2009) · Blood · doi:10.1182/blood-2009-04-217901 · Cited by 143
The IgH Locus 3′ Regulatory Region
Pinaud, E., Marquet, M., Fiancette, R., Péron, S., Vincent‐Fabert, C., Denizot, Y., & Cogné, M. (2011) · Advances in immunology · doi:10.1016/b978-0-12-387663-8.00002-8 · Cited by 134
van den Akker, E., Satchwell, T. J., Pellegrin, S., Daniels, G. L., & Toye, A. M. (2010) · Haematologica · doi:10.3324/haematol.2009.019828 · Cited by 133
FARBER, M., Koshy, M., KINNEY, T., & THECOOPERATIVESTUDYOFSICKLECE (1985) · Journal of Chronic Diseases · doi:10.1016/0021-9681(85)90033-5 · Cited by 122
Joining the loops: β‐Globin gene regulation
Noordermeer, D., & de Laat, W. L. (2008) · IUBMB Life · doi:10.1002/iub.129 · Cited by 95
McDevitt, M. A., Fujiwara, Y., Shivdasani, R. A., & Orkin, S. H. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.7976 · Cited by 94
Self-citationBhatnagar, P., Purvis, S. H., Barron‐Casella, E. A., DeBaun, M. R., Casella, J. F., Arking, D. E., & Keefer, J. R. (2011) · Journal of Human Genetics · doi:10.1038/jhg.2011.12 · Cited by 89
Bae, H. T., Baldwin, C. T., Paola Sebastiani, B., Telen, M. J., Ashley‐Koch, A. E., Garrett, M. E., Hooper, W. C., Bean, C. J., DeBaun, M. R., Arking, D. E., et al. (2012) · Blood · doi:10.1182/blood-2012-06-432849 · Cited by 84
John, A., Brylka, H., Wiegreffe, C., Simon, R., Liu, P., Jüttner, R., Crenshaw, E. B., Luyten, F. P., Jenkins, N. A., Copeland, N. G., et al. (2012) · Development · doi:10.1242/dev.072850 · Cited by 72
Erythropoiesis and globin switching in compound Klf1::Bcl11a mutant mice
Esteghamat, F., Gillemans, N., Bilić, I., van den Akker, E., Cantú, I., van Gent, T., Klingmüller, U., van Lom, K., Lindern, M. V., Grosveld, F. G., et al. (2013) · Blood · doi:10.1182/blood-2012-06-434530 · Cited by 52
John van der, O. O. S. T. (2013) · Science · doi:10.1126/science.1234726 · Cited by 48
Paul, D. S., Nisbet, J. P., Yang, T.-P., Meacham, S., Rendon, A., Hautaviita, K., Tallila, J., White, J. K., Tijssen, M. R., Sivapalaratnam, S., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002139 · Cited by 46
Chapter 5 Long‐Range Regulation of α‐Globin Gene Expression
Higgs, D. R., Vernimmen, D., & Wood, B. (2008) · Advances in genetics · doi:10.1016/s0065-2660(07)00005-3 · Cited by 32
Genomewide Association Studies and Common Disease — Realizing Clinical Utility
Fugger, L. H., McVean, G., & Bell, J. I. (2012) · New England Journal of Medicine · doi:10.1056/nejmp1212285 · Cited by 31
Turner, D. J., & Hurles, M. E. (2009) · Nature Protocols · doi:10.1038/nprot.2009.184 · Cited by 18
Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR
Tyson, J., & Armour, J. A. L. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-693 · Cited by 5
Cited by
Sorted by citations
CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
Frangoul, H., Altshuler, D., Cappellini, M. D., Chen, Y.-S., Domm, J., Eustace, B. K., Foell, J., de la Fuente, J., Grupp, S., Handgretinger, R., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2031054 · Cited by 1,962
Piel, F. B., Steinberg, M. H., & Rees, D. C. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1510865 · Cited by 1,488
Therapeutic genome editing: prospects and challenges
Cox, D. B. T., Platt, R. J., & Zhang, F. (2015) · Nature Medicine · doi:10.1038/nm.3793 · Cited by 1,336
Gene therapy returns to centre stage
Naldini, L. (2015) · Nature · doi:10.1038/nature15818 · Cited by 1,184
Long-range enhancer–promoter contacts in gene expression control
Schoenfelder, S., & Fraser, P. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0128-0 · Cited by 1,102
Metadata
- 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.
- ORCID
- Venue
- Science
- Published
- 2013-10-11
- Volume
- 342
- Issue
- 6155
- Pages
- 253-257
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4018826
- OpenAlex
- W2008989169
- Semantic Scholar
- 2845316815fa241ea105cf77d04cc6906bf4c64b
- 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
- green
- europepmc.org
- 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 (clinical) › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
