The DOI matches its Crossref record; 70 of the 71 references it cites were found in a registry or an index.
Transcriptional silencing of γ-globin by BCL11A involves long-range interactions and cooperation with SOX6
Open accessAbstract
The developmental switch from human fetal (γ) to adult (β) hemoglobin represents a clinically important example of developmental gene regulation. The transcription factor BCL11A is a central mediator of γ-globin silencing and hemoglobin switching. Here we determine chromatin occupancy of BCL11A at the human β-globin locus and other genomic regions in vivo by high-resolution chromatin immunoprecipitation (ChIP)–chip analysis. BCL11A binds the upstream locus control region (LCR), ɛ-globin, and the intergenic regions between γ-globin and δ-globin genes. A chromosome conformation capture (3C) assay shows that BCL11A reconfigures the β-globin cluster by modulating chromosomal loop formation. We also show that BCL11A and the HMG-box-containing transcription factor SOX6 interact physically and functionally during erythroid maturation. BCL11A and SOX6 co-occupy the human β-globin cluster along with GATA1, and cooperate in silencing γ-globin transcription in adult human erythroid progenitors. These findings collectively demonstrate that transcriptional silencing of γ-globin genes by BCL11A involves long-range interactions and cooperation with SOX6. Our findings provide insight into the mechanism of BCL11A action and new clues for the developmental gene regulatory programs that function at the β-globin locus.
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 cited source says what the claim attributes to it.
In the citing paper
“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 [6]
The cited source says what the claim attributes to it.
In the citing paper
“Further molecular studies revealed that BCL11A interacts with several erythroid regulators including GATA1, FOG1, and SOX6, and with the nucleosome remodeling and deacetylase complex (NuRD) (4, 6).”
From Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A (2013) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“In control cells, ChIP analysis revealed that BCL11A occupies several discrete regions within the human β -globin cluster, including the DNase I hypersensitive site 3 (HS3) within the locus control region (LCR), the e -globin promoter, and the γδ -intergenic region, consistent with previous analyses (4, 6).”
From Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A (2013) · cites this paper as [6]
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
The Role of Chromatin during Transcription
Li, B., Carey, M., & Workman, J. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.015 · Cited by 3,503
The ENCODE (ENCyclopedia Of DNA Elements) Project
(2004) · Science · doi:10.1126/science.1105136 · Cited by 2,390
Position-independent, high-level expression of the human β-globin gene in transgenic mice
Grosveld, F. G., van Assendelft, G. B., Greaves, D. R., & Kollias, G. A. (1987) · Cell · doi:10.1016/0092-8674(87)90584-8 · Cited by 1,908
The UCSC Genome Browser Database
Karolchik, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg129 · Cited by 1,890
A Lentiviral RNAi Library for Human and Mouse Genes Applied to an Arrayed Viral High-Content Screen
Moffat, J., Grueneberg, D. A., Yang, X., Kim, S. Y., Kloepfer, A. M., Hinkle, G., Piqani, B., Eisenhaure, T., Luo, B., Grenier, J. K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.01.040 · Cited by 1,804
Simonis, M., Klous, P., Splinter, E., Moshkin, Y., Willemsen, R., de Wit, E., van Steensel, B., & de Laat, W. (2006) · Nature Genetics · doi:10.1038/ng1896 · Cited by 1,386
Looping and Interaction between Hypersensitive Sites in the Active β-globin Locus
Tolhuis, B., Palstra, R.-J., Splinter, E., Grosveld, F., & de Laat, W. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00781-5 · Cited by 1,344
FoxA1 Translates Epigenetic Signatures into Enhancer-Driven Lineage-Specific Transcription
Lupien, M., Eeckhoute, J., Meyer, C. A., Wang, Q., Zhang, Y., Li, W., Carroll, J. S., Liu, X. S., & Brown, M. (2008) · Cell · doi:10.1016/j.cell.2008.01.018 · Cited by 983
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-citationFrom head to toes: the multiple facets of Sox proteins
Wegner, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.6.1409 · Cited by 890
Flagged first, then by citations
1 of the 71 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 301–361 of 361
BCL11Acontrôle l’expression de l’hémoglobine fœtale
Labie, D. (2012) · médecine/sciences · doi:10.1051/medsci/20122811007 · Cited by 2
HbA2: at the borderline of the KLF
Gallagher, P. G. (2011) · Blood · doi:10.1182/blood-2011-08-373324 · Cited by 2
Modifiers of γ-Globin Gene Expression and Treatment of β-Thalassemia
Munshi, A., Dadeech, S., Babu, M. S., & Khetarpal, P. (2015) · InTech eBooks · doi:10.5772/61441 · Cited by 2
Using microarray analysis to identify genes and pathways that regulate fetal hemoglobin levels
Jia, S., Jia, W., Yu, S., Hu, Y., & He, Y. (2019) · Annals of Human Genetics · doi:10.1111/ahg.12346 · Cited by 2
Gao, J., Liu, J., Zhang, L., Zhang, Y., Guo, Q., Li, Y., Tong, J., Wang, H., Zhou, J., Zhu, F., et al. (2019) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.111780 · Cited by 2
Recent perspectives of pediatric β-thalassemia
An, Q., Fan, C., & Xu, S. (2022) · Minerva Pediatrics · doi:10.23736/s2724-5276.18.04872-7 · Cited by 2
The Novel Role of the B-Cell Lymphoma/Leukemia 11A (BCL11A) Gene in β-Thalassaemia Treatment
Lai, M. I., & Ahmed, N. H. M. (2022) · Cardiovascular & Haematological Disorders - Drug Targets · doi:10.2174/1871529x23666230123140926 · Cited by 3
Suwito, B. E., Adji, A. S., Widjaja, J. S., Angel, S. C. S., Hajiri, A. Z. Z. A., Salamy, N. F. W., & Choirotussanijjah, C. (2023) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2023.11435 · Cited by 3
The histone methyltransferase MLL1 complex inhibits expression of fetal hemoglobin
Han, Y., Gudmundsdottir, B., Gudmundsson, K. O., Roy, K. R., Tisdale, J. F., & Du, Y. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110863 · Cited by 1
Jang, Y., Eom, Y. J., Gwak, S.-H., Koh, Y., Han, J., Rim, Y. A., Nam, Y., & Ju, J. H. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04825-1 · Cited by 2
Chumchuen, S., Pornsukjantra, T., Innachai, P., Khamphikham, P., Wongborisuth, C., Anurathapan, U., Songdej, D., Sripichai, O., Tangprasittipap, A., & Hongeng, S. (2025) · Scientific Reports · doi:10.1038/s41598-025-30762-3 · Cited by 2
Fetal Hemoglobin Research and Clinical Relevance in Sickle Cell Disease
Gudmundsdóttir, B. K., & Tisdale, J. F. (2025) · Physiology · doi:10.1152/physiol.00024.2025 · Cited by 1
Alotaibi, D., Aldagdog, F., Alramadhan, S. I., Almuhaidib, B., Asiri, N., Almodhi, L., Alshabaan, M., Alborhan, R., Vatte, C., Mohiuddin, S. S., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27031203 · Cited by 2
Mechanistic and Biological Perspectives on Erythropoiesis
Bresnick, E. H., Papayannopoulou, T., & Migliaccio, A. R. (2024) · Experimental Hematology · doi:10.1016/j.exphem.2024.104286 · Cited by 1
Suali, L., Salih, F. A. M., Ibrahim, M. Y., Jeffree, M. S., Suali, E., Moy, F. S., Fe, Y. S., & Sunggip, C. (2025) · Hemoglobin · doi:10.1080/03630269.2024.2448175 · Cited by 1
WGCNA and LASSO regression-based selection and validation of microRNA biomarkers of β-thalassemia
Yang, F., Shi, L., Su, S., Li, Y., Cheng, H., Liang, Z., Pang, L., & Lai, K. (2025) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2025.102957 · Cited by 1
Genomic Study in β-Thalassemia
Svasti, S., Sripichai, O., Nuinoon, M., Winichagoon, P., & Fucharoe, S. (2011) · InTech eBooks · doi:10.5772/23545 · Cited by 1
Chang, K., Huang, A., Han, H., Jiang, Y., Fang, X., Song, C.-Z., Padilla, S., Wang, H., Qu, H., Stamatoyannopoulos, J. A., et al. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.08.005 · Cited by 1
Mohammadi, Z., Mohammadi, R., Haghpanah, S., Moghadam, M., Pazhoomand, R., & Karimi, M. (2020) · Hemoglobin · doi:10.1080/03630269.2020.1845722 · Cited by 1
Liu, L., & Pertsemlidis, A. (2016) · The Medicine Forum · Cited by 1
Enhancer-dependence of gene expression increases with developmental agePreprint
Cai, W., Huang, J., Zhu, Q., Li, B. E., Seruggia, D., Zhou, P., Nguyen, M., Fujiwara, Y., Xie, H., Yang, Z., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/678334 · Cited by 1
Self-citationDynamic activity of Erg promotes aging of the hematopoietic systemPreprint
Tanaka-Yano, M., Sugden, W. W., Wang, D., Badalamenti, B., Côté, P., Chin, D. H., Goldstein, J., George, S., Rodrigues-Luiz, G. F., da Rocha, E. L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.23.634563 · Cited by 1
Globin gene regulation for treating β-thalassemias: progress, obstacles and future
Saliba, A. N., Alameddine, R. S., Harb, A., & Taher, A. T. (2015) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2015.1074071
Singh, J. (2014) · D-Scholarship@Pitt (University of Pittsburgh)
Dutta, A., Karkashon, S., Raghupathy, R., Bhatia, H., Tesfa, L., & Little, J. A. (2010) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2010.10.013
The Role of ZBP-89 in Globin Regulation
Aghajanirefah, A. (2012) · RePub (Erasmus University Rotterdam)
Developmental Maturation within the Hematopoietic System
Arora, N. (2014) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Wakabayashi, A., & Sankaran, V. G. (2015) · Pediatric Research · doi:10.1038/pr.2015.245
Self-citationRole of Sox6 and Coup-TFII transcription factors in the regulation of hemoglobin switching
Elangovan, S. (2014) · BOA (University of Milano-Bicocca)
Durlak, M. (2015) · BOA (University of Milano-Bicocca)
Precision Medicine for Sickle Cell Disease: Discovery of Genetic Targets for Drug Development
Pace, B. S., Lopez, N. H., Zhu, X., & Li, Y. (2016) · InTech eBooks · doi:10.5772/64817 · Cited by 1
Hematopoietic Cell Transplantation for Sickle Cell Disease
Walters, M. C. (2015) · Wiley eBooks · doi:10.1002/9781118416426.ch72
Mehraei, M. (2016) · Eastern Mediterranean University Institutional Repository (Eastern Mediterranean University) · doi:10.13140/rg.2.2.13627.31526
In vitro CRISPR-mediated gamma globin gene activation in HEK293
Villacis, A. C. S., Ramasko, M. B., Richmond, L., & West, A. G. (2019) · MOL2NET International Conference on Multidisciplinary Sciences (MOL2NET) · doi:10.3390/mol2net-05-06384
MiR-144 Regulates Hemoglobin Expression in Human Erythroid Cell Line
Penglong, T., Saensuwanna, A., Kocharoenwat, J., BOORINTARAGOT, W., FUPONGSIRIPHAN, S., & Srinoun, K. (2020) · Walailak Journal of Science and Technology (WJST) · doi:10.48048/wjst.2020.10712
Derfoul, A., Pinal‐Fernandez, I., Huang, W., Parks, C., Pak, K. S., Hoffmann, V. J., Mammen, A. L., & Georgopoulos, K. (2020) · Research Square · doi:10.21203/rs.3.rs-112107/v1
Ferguson, D. C. J., MacInnes, K. A., Daniels, D. E., & Frayne, J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822230-0.00006-5
Blood components from pluripotent stem cells
Kimbrel, E. A., & Lanza, R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818422-6.00043-5
Mumtaz, K., Hussain, I., Iftikhar, F., Rehman, F. U., Jameel, M., Farooq, S., Hassan, H., Fatima, A., Ottmann, O. G., & Mian, A. A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.28.568974
Fibrillarin modulates fetal hemoglobin silencingPreprint
Wu, D., Li, Q., Qiu, S., Guo, C., Li, F., Shangguan, W., Li, W., Yang, D., Meng, X., Xing, M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.25.600532
MLL1 complex is a critical regulator of fetal hemoglobin repressionPreprint
Han, Y., Gudmundsdottir, B., Gudmundsson, K. O., Roy, K. R., Tisdale, J. F., & Du, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.24.645036
Dynamic activity of Erg promotes maturation of the hematopoietic system
Tanaka-Yano, M., Sugden, W. W., Wang, D., Falchetti, M., Badalamenti, B., Côté, P., Chin, D. H., Goldstein, J., George, S., Rodrigues-Luiz, G. F., et al. (2025) · Blood Advances · doi:10.1182/bloodadvances.2025017705 · Cited by 1
Luanpitpong, S., Kang, X., Janan, M., Thumanu, K., Li, J., Kheolamai, P., & Issaragrisil, S. (2022) · Figshare · doi:10.6084/m9.figshare.20145672
Luanpitpong, S., Kang, X., Janan, M., Thumanu, K., Li, J., Kheolamai, P., & Issaragrisil, S. (2022) · Figshare · doi:10.6084/m9.figshare.20145669
Pioneer Transcription Factors Differentially Co-opt Bcl11a and Bcl11b to orchestrate ReprogrammingPreprint
Trajkova, A., Zakiev, E., Mendoza-Ferri, M. G., Messahli, I., Ruel, M., Krossa, I., Tapponnier, Y., Dejonckere, E., Hunter, E., Claret, L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.19.694617
Identification of RBM3 as a novel regulator of human fetal hemoglobin expression
Ma, S., Liu, X., Qin, Y., Wang, Y., Feng, Y., Cheng, B., & Wang, L. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.116107
Younus, L. A., Al-Zubaidy, H. F. S., Abdulrudha, K. H., Nasser, F. A., & Kudhair, A. H. (2025) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-025-00824-2
Differential expression of m icroRNAs in cord blood exosomes regulating fetal haemoglobin expression
Ghosh, A., Prakash, S., Kiran, S., Das, P. G. S., Mukherjee, S., Singh, S., & Chhabra, G. (2026) · Vox Sanguinis · doi:10.1111/vox.70169
Near completely reversing the γ- to β-globin switch by enhancer release, retargeting and reinforcingPreprint
Wang, N., Yang, K., Xie, X., Cui, S., Pei, X., Zhao, X., Hao, D., Jia, Y., Yang, G., Liu, R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.30.702713
LDB1 represses fetal hemoglobin expression by enhancing BCL11A transcription
Park, S.-W., Choi, C., Park, I.-B., Kang, S. J., Lee, H. J., Kim, J.-I., Bae, J., Geum, D., Cheon, Y. P., & Chun, T. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104070
New therapeutic strategies for the treatment of β-hemoglobinopathies
Weber, L. (2018) · theses.fr (ABES) · doi:10.70675/09314463zdfd1z46b4z9c0cz32c6c2c5ccc2
Stage-specific changes in the Krebs cycle network regulate human erythroid differentiation
Romano, M. (2018) · theses.fr (ABES) · doi:10.70675/4312681cz0207z4923zb100z879f8a73681c
Base editing approaches for the treatment of β-hemoglobinopathies
Antoniou, P. (2021) · theses.fr (ABES) · doi:10.70675/c4dddb32zf8aez4bc3z8cf8zce9a4e808265
Development of gene therapy approaches to ß-hemoglobinopathies
Chalumeau, A. (2023) · theses.fr (ABES) · doi:10.70675/7fc1b037zbffbz4005z9109zd81aa6f38a83
Genome and epigenome editing approaches to treat β-hemoglobinopathies
Fontana, L. (2024) · theses.fr (ABES) · doi:10.70675/f1623d8bz5529z4d2dzb255z45ed273f643c
Modeling Therapeutic Targets: $$\beta $$-Globin Disorders and Beyond
Bashirov, R. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-20041-9_4
Yu, M., Das, P., Zhang, X., & Cheng, X. (2026) · Molecular Oncology · doi:10.1002/1878-0261.70304
Epigenetic strategies for fetal hemoglobin induction in sickle cell disease
de Souza, M. M., Pavan, A. R., Pastre, V. G. D. F., Gini, A. L. R., Silva, R. D. A., Lanaro, C., de Albuquerque, D. M., Costa, F. F., Scarim, C. B., Hodgkinson, J. T., et al. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119186 · Cited by 1
Schüler, L., Winkler, R. E., Gonçalves-Dias, J., Schuschel, K., Issa, H., Verboon, L., Wei, X., Çetin, R., Matthess, Y., Kaulich, M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.18.745242
BindingDB (2017) · UC San Diego · doi:10.7270/q2qz28tm
Cooperative Repression of γ-Globin by LYAR and NONO
Wu, D., Shangguan, W., Wang, X., Liu, T., Li, W., Liao, R., Meng, X., Xing, M., Zhu, Y., Zhang, R., et al. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113702
Metadata
- Authors
- Xu, J., Sankaran, V. G., Ni, M., Menne, T. F., Puram, R. V., Kim, W., & Orkin, S. H.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- Harvard–MIT Division of Health Sciences and Technology (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-04-15
- Volume
- 24
- Issue
- 8
- Pages
- 783-798
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2854393
- OpenAlex
- W2134881764
- Semantic Scholar
- 097ee5589990708503598c372d66d87bf5262280
- Cited by
- 361
- References
- 71
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 19 · 2023: 15 · 2022: 23 · 2021: 21 · 2020: 20 · 2019: 17 · 2018: 21 · 2017: 31 · 2016: 30 · 2015: 25 · 2014: 26 · 2013: 23 · 2012: 22
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Kay Kendall Leukaemia Fund
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL032259, T32HL116324)
- National Cancer Institute (K12CA087723)
- National Institute of General Medical Sciences (T32GM007753)
- National Institute of Diabetes and Digestive and Kidney Diseases
- 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 › Biochemistry › Hemoglobin structure and function
- Keywords
- BCL11A, SOX6, beta-globin locus, hemoglobin switching, long-range chromatin interactions, chromatin looping, locus control region, erythroid maturation, GATA-1, erythroid progenitor cells, developmental gene regulation, chromatin occupancy
- MeSH terms
- Adult, Animals, Carrier Proteins, Cell Line, Erythropoiesis, Histones, Humans, Nuclear Proteins, Protein Binding, Repressor Proteins, Gene Expression Regulation, Developmental, Gene Silencing, Protein Transport, Erythroid Cells, GATA1 Transcription Factor, Mice, gamma-Globins, SOXD Transcription Factors
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
