The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin
Open accessAbstract
Reactivating the fetal globin gene: Mutation of adult-type globin genes causes sickle cell disease and thalassemia. Although treating these hemoglobinopathies with gene therapy is possible, there is a pressing need for pharmacologic approaches to treat general patient populations. One promising approach is to reactivate repressed expression of fetal-type hemoglobin (HbF) in adult erythroid cells. Masuda et al. reveal a molecular mechanism governing HbF repression as mediated by the LRF/ZBTB7A transcription factor. The study may encourage the development of new HbF reactivation therapies for hemoglobinopathies. Science , this issue p. 285
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
“Its inactivation in HUDEP-2 cells led to ;50% HbF; BCL11A plus ZBTB7A knockout caused .90% HbF. 25”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [25]
Experimental — accuracy not yet measured
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
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013) · Nature Methods · doi:10.1038/nmeth.2688 · Cited by 6,422
Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
Bailey, T. L., & Elkan, C. (1994) · PubMed · Cited by 4,982
In-gel digestion for mass spectrometric characterization of proteins and proteomes
Shevchenko, A., Tomas, H., Havli, J., Olsen, J. V., & Mann, M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.468 · Cited by 4,947
ATAC-seq: a method for assaying chromatin accessibility genome-wide
Buenrostro, J. D., Wu, B., Chang, H. Y., & Greenleaf, W. J. (2015) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb2129s109 · Cited by 3,289
TRANSFAC(R) and its module TRANSCompel(R): transcriptional gene regulation in eukaryotes
Matys, V. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj143 · Cited by 2,142
Quantifying similarity between motifs
Gupta, S., Stamatoyannopoulos, J. A., Bailey, T. L., & Noble, W. S. (2007) · Genome Biology · doi:10.1186/gb-2007-8-2-r24 · Cited by 2,058
Mammalian Ras interacts directly with the serine/threonine kinase raf
Vojtek, A. B., Hollenberg, S. M., & Cooper, J. A. (1993) · Cell · doi:10.1016/0092-8674(93)90307-c · Cited by 1,934
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
Piel, F. B., Hay, S. I., Gupta, S., Weatherall, D. J., & Williams, T. N. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001484 · Cited by 1,144
Jackson, A. L., & Linsley, P. S. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd3010 · Cited by 1,124
DREME: motif discovery in transcription factor ChIP-seq data
Bailey, T. L. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr261 · Cited by 1,007
Mathelier, A., Zhao, X., Zhang, A. W., Parcy, F., Worsley-Hunt, R., Arenillas, D. J., Buchman, S., Chen, C., Chou, A., Ienasescu, H., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt997 · 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-citationDesign and analysis of ChIP-seq experiments for DNA-binding proteins
Kharchenko, P. V., Tolstorukov, M. Y., & Park, P. J. (2008) · Nature Biotechnology · doi:10.1038/nbt.1508 · Cited by 914
Self-citationBCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
Canver, M. C., Smith, E. C., Sher, F., Pinello, L., Sanjana, N. E., Shalem, O., Chen, D. D., Schupp, P. G., Vinjamur, D. S., Garcia, S. P., et al. (2015) · Nature · doi:10.1038/nature15521 · Cited by 886
Self-citationDeng, W., Lee, J., Wang, H., Miller, J., Reik, A., Gregory, P. D., Dean, A., & Blobel, G. A. (2012) · Cell · doi:10.1016/j.cell.2012.03.051 · Cited by 734
Defining functional DNA elements in the human genome
Kellis, M., Wold, B. J., Snyder, M. P., Bernstein, B., Kundaje, A. B., Marinov, G. K., Ward, L. D., Birney, E., Crawford, G. E., Dekker, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318948111 · Cited by 720
Inferring direct DNA binding from ChIP-seq
Bailey, T. L., & Machanick, P. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks433 · Cited by 472
Yıldırım, Ö., Li, R., Hung, J., Chen, P. B., Dong, X., Ee, L.-S., Weng, Z., Rando, O. J., & Fazzio, T. G. (2011) · Cell · doi:10.1016/j.cell.2011.11.054 · Cited by 463
Kurita, R., Suda, N., Sudo, K., Miharada, K., Hiroyama, T., Miyoshi, H., Tani, K., & Nakamura, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059890 · Cited by 418
Self-citationRole of the proto-oncogene Pokemon in cellular transformation and ARF repression
Maeda, T., Hobbs, R. M., Merghoub, T., Guernah, I., Zelent, A., Cordon‐Cardo, C., Teruya‐Feldstein, J., & Pandolfi, P. P. (2005) · Nature · doi:10.1038/nature03203 · Cited by 401
Self-citationControl of globin gene expression during development and erythroid differentiation
Stamatoyannopoulos, G. (2005) · Experimental Hematology · doi:10.1016/j.exphem.2004.11.007 · Cited by 393
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-citationGlobal transcriptome analyses of human and murine terminal erythroid differentiation
An, X., Schulz, V., Li, J., Wu, K., Liu, J., Xue, F., Hu, J., Mohandas, N., & Gallagher, P. G. (2014) · Blood · doi:10.1182/blood-2014-01-548305 · Cited by 361
Xu, 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-citationCanver, M. C., Bauer, D. E., Dass, A., Yien, Y. Y., Chung, J., Masuda, T., Maeda, T., Paw, B. H., & Orkin, S. H. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.564625 · Cited by 357
Self-citationCorrection 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-citationPolo, J. M., Dell’Oso, T., Ranuncolo, S. M., Cerchietti, L. C. A., Beck, D. B., da Silva, G. F., Privé, G. G., Licht, J. D., & Melnick, A. M. (2004) · Nature Medicine · doi:10.1038/nm1134 · Cited by 291
A Small-Molecule Inhibitor of BCL6 Kills DLBCL Cells In Vitro and In Vivo
Cerchietti, L. C., Ghetu, A. F., Zhu, X., Da Silva, G. F., Zhong, S., Matthews, M., Bunting, K. L., Polo, J. M., Farès, C., Arrowsmith, C. H., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.050 · Cited by 288
Chan, I. T., Kutok, J. L., Williams, I. R., Cohen, S., Kelly, L., Shigematsu, H., Johnson, L., Akashi, K., Tuveson, D. A., Jacks, T., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20476 · Cited by 270
Yolk sac–derived primitive erythroblasts enucleate during mammalian embryogenesis
Kingsley, P. D., Malik, J. T., Fantauzzo, K. A., & Palis, J. (2004) · Blood · doi:10.1182/blood-2003-12-4162 · Cited by 253
A positive role for NLI/Ldb1 in long-range β-globin locus control region function
Song, S.-H., Hou, C., & Dean, A. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.09.025 · Cited by 233
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-citationPeterson, K. R., Clegg, C. H., Huxley, C. M., Josephson, B. M., Haugen, H. S., Furukawa, T., & Stamatoyannopoulos, G. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.16.7593 · Cited by 222
Regulation of B Versus T Lymphoid Lineage Fate Decision by the Proto-Oncogene LRF
Maeda, T., Merghoub, T., Hobbs, R. M., Dong, L., Maeda, M., Zakrzewski, J. L., van den Brink, M. R. M., Zelent, A., Shigematsu, H., Akashi, K., et al. (2007) · Science · doi:10.1126/science.1140881 · Cited by 213
Self-citationConservation of trans-acting circuitry during mammalian regulatory evolution
Stergachis, A. B., Neph, S., Sandstrom, R., Haugen, E., Reynolds, A. P., Zhang, M., Byron, R., Canfield, T., Stelhing-Sun, S., Lee, K., et al. (2014) · Nature · doi:10.1038/nature13972 · Cited by 212
The embryonic origins of erythropoiesis in mammals
Baron, M. H., Isern, J., & Fraser, S. T. (2012) · Blood · doi:10.1182/blood-2012-01-153486 · Cited by 209
BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR–ABL1 kinase inhibition
Duy, C., Hurtz, C., Shojaee, S., Cerchietti, L. C. A., Geng, H., Swaminathan, S., Klemm, L., Kweon, S.-M., Nahar, R. R., Braig, M., et al. (2011) · Nature · doi:10.1038/nature09883 · Cited by 204
An embryonic pattern of expression of a human fetal globin gene in transgenic mice
Chada, K. K., Magram, J., & Costantini, F. D. (1986) · Nature · doi:10.1038/319685a0 · Cited by 198
Isolation and transcriptome analyses of human erythroid progenitors: BFU-E and CFU-E
Li, J., Hale, J., Bhagia, P., Xue, F., Chen, L., Jaffray, J., Yan, H., Lane, J. M., Gallagher, P. G., Mohandas, N., et al. (2014) · Blood · doi:10.1182/blood-2014-07-588806 · Cited by 190
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-citationPuromycin-sensitive Aminopeptidase
Constam, D. B., Tobler, A. R., Rensing‐Ehl, A., Kemler, I., Hersh, L. B., & Fontana, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.26931 · Cited by 174
Structure of a BCOR Corepressor Peptide in Complex with the BCL6 BTB Domain Dimer
Ghetu, A. F., Corcoran, C. M., Cerchietti, L., Bardwell, V. J., Melnick, A., & Privé, G. G. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.12.026 · Cited by 168
“Maturational” globin switching in primary primitive erythroid cells
Kingsley, P. D., Malik, J. T., Emerson, R. L., Bushnell, T. P., McGrath, K. E., Bloedorn, L. A., Bulger, M., & Palis, J. (2005) · Blood · doi:10.1182/blood-2005-08-3097 · Cited by 165
POK/ZBTB proteins: an emerging family of proteins that regulate lymphoid development and function
Lee, S., & Maeda, T. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01116.x · Cited by 153
Self-citationAn enhancer element lies 3′ to the human A gamma globin gene.
Bodine, D. M., & Ley, T. J. (1987) · The EMBO Journal · doi:10.1002/j.1460-2075.1987.tb02605.x · Cited by 126
Maeda, T., Ito, K., Merghoub, T., Poliseno, L., Hobbs, R. M., Wang, G., Dong, L., Maeda, M., Doré, L. C., Zelent, A., et al. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.09.005 · Cited by 115
Self-citationMBD3 Localizes at Promoters, Gene Bodies and Enhancers of Active Genes
Shimbo, T., Du, Y., Grimm, S. A., Dhasarathy, A., Mav, D., Shah, R., Shi, H., & Wade, P. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1004028 · Cited by 115
Mi2β-mediated silencing of the fetal γ-globin gene in adult erythroid cells
Amaya, M., Desai, M., Gnanapragasam, M. N., Wang, S. Z., Zu Zhu, S., Williams, D. C., & Ginder, G. D. (2013) · Blood · doi:10.1182/blood-2012-11-466227 · Cited by 102
Kramer, H., Lavender, K. J., Li, Q., Stacey, A., Liu, M. K. P., di Gleria, K., Simmons, A., Gasper-Smith, N., Haynes, B. F., McMichael, A. J., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000893 · Cited by 99
Methyl binding domain protein 2 mediates γ-globin gene silencing in adult human βYAC transgenic mice
Rupon, J. W., Wang, S. Z., Gaensler, K. M. L., Lloyd, J. A., & Ginder, G. D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509322103 · Cited by 74
Molecular characterization of a puromycin‐insensitive leucyl‐specific aminopeptidase, PILS‐AP
Schomburg, L., Kollmus, H., Friedrichsen, S., & Bauer, K. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01348.x · Cited by 65
Pleasants, S. (2014) · Nature · doi:10.1038/515s2a · Cited by 65
LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem cell maintenance
Lee, S.-U., Maeda, M., Ishikawa, Y., Li, S. M., Wilson, A., Jubb, A. M., Sakurai, N., Weng, L., Fiorini, E., Radtke, F., et al. (2012) · Blood · doi:10.1182/blood-2012-03-418103 · Cited by 55
Self-citationIdentification of Biologically Relevant Enhancers in Human Erythroid Cells
Su, M. Y., Steiner, L. A., Bogardus, H. H., Mishra, T., Schulz, V., Hardison, R. C., & Gallagher, P. G. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.413260 · Cited by 49
Ulirsch, J. C., Lacy, J. N., An, X., Mohandas, N., Mikkelsen, T. S., & Sankaran, V. G. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004890 · Cited by 49
Role of the GATA-1/FOG-1/NuRD Pathway in the Expression of Human β-Like Globin Genes
Miccio, A., & Blobel, G. A. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00001-10 · Cited by 48
Role of the clathrin adaptor PICALM in normal hematopoiesis and polycythemia vera pathophysiology
Ishikawa, Y., Maeda, M., Pasham, M. R., Aguet, F., Tacheva-Grigorova, S. K., Masuda, T., Yi, H. F., Lee, S.-U., Xu, J., Teruya‐Feldstein, J., et al. (2014) · Haematologica · doi:10.3324/haematol.2014.119537 · Cited by 44
Self-citationSakurai, N., Maeda, M., Lee, S.-U., Ishikawa, Y., Li, M., Williams, J. C., Wang, L., Su, L., Suzuki, M., Saito, T. I., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45682 · Cited by 42
Self-citationIsoelectric Focusing in Agarose Gel for Detection and Identification of Hemoglobin Variants
Black, J. (1984) · Hemoglobin · doi:10.3109/03630268408991705 · Cited by 23
Cited by
Sorted by citations
Piel, F. B., Steinberg, M. H., & Rees, D. C. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1510865 · Cited by 1,488
Piel, F. B., Steinberg, M., & Rees, D. C. (2016) · Spiral (Imperial College London) · doi:10.1056/nejmc1706325#sa6 · Cited by 662
Martyn, G. E., Wienert, B., Yang, L., Shah, M., Norton, L. J., Burdach, J., Kurita, R., Nakamura, Y., Pearson, R. C. M., Funnell, A. P. W., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0085-0 · Cited by 300
Self-citationMolecular basis of β thalassemia and potential therapeutic targets
Thein, S. L. (2017) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2017.06.001 · Cited by 219
“In double knockout cells, HbF comprised> 90% of total hemoglobin suggesting that the silencing pathway of LRF is independent of BCL11A [131].”
Recent Advances in the Treatment of Sickle Cell Disease
Cisneros, G. S., & Thein, S. L. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00435 · Cited by 210
“Disrupting the putative binding sites for γ-globin repressors like BCL11A to induce HbF production will be an attractive therapeutic strategy for both β-thalassemic and SCD patients (Masuda et al., 2016; Liu et al., 2018; Martyn et al., 2018).”
Background
Metadata
- Authors
- Masuda, T., Wang, X., Maeda, M., Canver, M. C., Sher, F., Funnell, A. P. W., Fisher, C., Suciu, M., Martyn, G. E., Norton, L. J., Zhu, C., Kurita, R., Nakamura, Y., Xu, J., Higgs, D. R., Crossley, M., Bauer, D. E., Orkin, S. H., Kharchenko, P. V., & Maeda, T.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Boston Children's Hospital (US)
- UNSW Sydney (AU)
- Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
- University of Oxford (GB)
- RIKEN BioResource Research Center (JP)
- University of Tsukuba (JP)
- Corresponding author
- Kharchenko, Peter V.
- Maeda, Takahiro
- ORCID
- Venue
- Science
- Published
- 2016-01-15
- Volume
- 351
- Issue
- 6270
- Pages
- 285-289
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4778394
- OpenAlex
- W2266790363
- Semantic Scholar
- c79067255bc10df384cd93d45af5c2fd24b7b528
- Cited by
- 373
- References
- 64
- Citations by year
- 2026: 27 · 2025: 34 · 2024: 51 · 2023: 34 · 2022: 34 · 2021: 54 · 2020: 44 · 2019: 24 · 2018: 26 · 2017: 27 · 2016: 16
- FWCI
- 22.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (F30DK103359-01A1)
- NIDDK Career Development (K08DK093705)
- Doris Duke Charitable Foundation Innovations in Clinical Research (2013137)
- Ellison Medical Foundation (AG-NS-0965-12)
- NIH (P01HL032262, P30DK049216, 5K25AG037596, R01 AI084905, R56 DK105001)
- American Society of Hematology Bridge Program
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- fetal hemoglobin, BCL11A, transcriptional repression, nucleosome density, sickle cell disease, thalassemia, hemoglobinopathies, fetal hemoglobin induction
- MeSH terms
- Anemia, Sickle Cell, Animals, Carrier Proteins, Cell Line, Chromatin, DNA-Binding Proteins, Erythroblasts, Erythropoiesis, Fetal Hemoglobin, Humans, Nuclear Proteins, Repressor Proteins, Thalassemia, Transcription Factors, Sequence Deletion, Mice, Knockout, Gene Silencing, Mice, gamma-Globins
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
