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
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Inactivation of ZBTB7A in HUDEP-2 cells led to approximately 50% HbF, and BCL11A plus ZBTB7A knockout caused more than 90% HbF.
“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]
The HUDEP-2 results report HbF above 60% in all three ZBTB7A-knockout clones, not approximately 50%. The double-knockout results report HbF at 91–94% of total hemoglobin, supporting the second figure. (LLM, conf=0.91)
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Lentiviral and genome-editing strategies for the treatment of β-hemoglobinopathies
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ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression
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“A better understanding of transcriptional regulators such as BCL11A, provides genomic-based approaches for prevention of switching or reactivation of fetal hemoglobin production [209,210].”
BackgroundTranscription factor competition at the γ-globin promoters controls hemoglobin switching
Liu, N., Xu, S., Yao, Q., Zhu, Q., Yan, K., Hsu, J. Y., Sakon, P., Pinello, L., Yuan, G., Bauer, D. E., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00798-y · Cited by 86 · see citing works
Self-citationTherapeutic adenine base editing of human hematopoietic stem cells
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Self-citationFetal haemoglobin induction in sickle cell disease
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“, Maeda, T., Yuan, G.C., Zhang, F., Orkin, S.H. & Bauer, D.E. (2015) BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis.”
BackgroundInfluentialRegulation of hematopoietic development by ZBTB transcription factors
Maeda, T. (2016) · International Journal of Hematology · doi:10.1007/s12185-016-2035-x · Cited by 85 · see citing works
“A yeast twohybrid screen using the LRF-BTB domain as bait identified a series of transcriptional regulators, including NuRD subunits and chromatin remodelers, as interacting proteins [47].”
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Potent and uniform fetal hemoglobin induction via base editing
Mayuranathan, T., Newby, G. A., Feng, R., Yao, Y., Mayberry, K. D., Lazzarotto, C. R., Li, Y., Levine, R. M., Nimmagadda, N., Dempsey, E., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01434-7 · Cited by 83 · see citing works
Self-citationZNF410 represses fetal globin by singular control of CHD4
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Self-citationβ-Thalassemia intermedia: a comprehensive overview and novel approaches
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Molecular Basis and Genetic Modifiers of Thalassemia
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Non-deletional alpha thalassaemia: a review
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An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility
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“HUDEP-2 cells are an in vitro model of human erythropoiesis that mimics erythroid development from the proerythroblast to reticulocyte stages (21, 35).”
BackgroundSelf-citationMartyn, G. E., Wienert, B., Kurita, R., Nakamura, Y., Quinlan, K. G. R., & Crossley, M. (2019) · Blood · doi:10.1182/blood-2018-07-863951 · Cited by 75 · see citing works
Self-citationIn vitro and in vivo induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor
Gilmartin, A. G., Groy, A., Gore, E. R., Atkins, C. L., Long, E. R., Montoute, M. N., Wu, Z., Halsey, W. S., McNulty, D. E., Ennulat, D., et al. (2020) · Haematologica · doi:10.3324/haematol.2020.248658 · Cited by 72 · see citing works
“(4-6) The repressor complexes cause significant”
Li, C., Wang, H., Georgakopoulou, A., Gil, S., Yannaki, E., & Lieber, A. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.09.001 · Cited by 73 · see citing works
“29 No 2 February 2021 and HBG genes is blocked by proteins, including BCL11A.(22,46) When this blockade is weakened, e.”
BackgroundLi, C., Psatha, N., Gil, S., Wang, H., Papayannopoulou, T., & Lieber, A. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.04.008 · Cited by 71 · see citing works
Activation of γ-globin expression by hypoxia-inducible factor 1α
Feng, R., Mayuranathan, T., Huang, P., Doerfler, P. A., Li, Y., Yao, Y., Zhang, J., Palmer, L. E., Mayberry, K. D., Christakopoulos, G. E., et al. (2022) · Nature · doi:10.1038/s41586-022-05312-w · Cited by 69 · see citing works
KLF1 directly activates expression of the novel fetal globin repressor ZBTB7A/LRF in erythroid cells
Norton, L. J., Funnell, A. P. W., Burdach, J., Wienert, B., Kurita, R., Nakamura, Y., Philipsen, S., Pearson, R. C. M., Quinlan, K. G. R., & Crossley, M. (2017) · Blood Advances · doi:10.1182/bloodadvances.2016002303 · Cited by 65 · see citing works
“Inactivation of ZBTB7A derepressed g-globin expression in a humanized transgenic mouse model, as well as in human cells, and ZBTB7A normally represses expression of the g-globin genes.(7) ZBTB7A represses g-globin expression by recruiting a unique NuRD repressor complex, independently of BCL11A.”
BackgroundSelf-citationCRISPR/Cas9 for Sickle Cell Disease: Applications, Future Possibilities, and Challenges
Demirci, S., Leonard, A. K., Haro‐Mora, J. J., Uchida, N., & Tisdale, J. F. (2019) · Advances in experimental medicine and biology · doi:10.1007/5584_2018_331 · Cited by 67 · see citing works
Emerging role of ZBTB7A as an oncogenic driver and transcriptional repressor
Gupta, S., Singh, A. K., Prajapati, K. S., Kushwaha, P. P., Shuaib, M., & Kumar, S. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.04.015 · Cited by 65 · see citing works
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Self-citationCustomizing the genome as therapy for the β-hemoglobinopathies.
Canver, M. C., & Orkin, S. H. (2016) · Blood · doi:10.1182/blood-2016-01-678128 · Cited by 61 · see citing works
Self-citationYu, X., Azzo, A., Bilinovich, S. M., Li, X., Dozmorov, M. G., Kurita, R., Nakamura, Y., Williams, D. C., & Ginder, G. D. (2019) · Haematologica · doi:10.3324/haematol.2018.210963 · Cited by 57 · see citing works
“With a β/g-globin expression profile of <1% g-globin and >95% β-globin, very similar to adult erythroid cells, the HUDEP-2 line has become a useful model system for studying globin switching.(11,13,38) Based on the 10-20-fold increase in g-globin gene expression in β-YAC mice lacking MBD2,(32) we hypothesized that the…”
BackgroundMethodResultInfluentialSelf-citationSingle-nucleotide-level mapping of DNA regulatory elements that control fetal hemoglobin expression
Cheng, L., Li, Y., Qi, Q., Xu, P., Feng, R., Palmer, L. E., Chen, J., Wu, R., Yee, T., Zhang, J., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00861-8 · Cited by 56 · see citing works
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Self-citationLeighton, G. O., & Williams, D. C. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.007 · Cited by 53 · see citing works
“Similarly, Takahiro Maeda’s group found that the ZBTB7A transcription factor (also known as LRF) binds to the γ-globin locus and recruits NuRD to silence gene expression [50].”
BackgroundThalassemias: from gene to therapy
Simone, G. D., Quattrocchi, A., Mancini, B., di Masi, A., Nervi, C., & Ascenzi, P. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.101028 · Cited by 55 · see citing works
Reactivation of a developmentally silenced embryonic globin gene
King, A. J., Songdej, D., Downes, D. J., Beagrie, R. A., Liu, S., Buckley, M., Peng, H., Suciu, M., Oudelaar, A. M., Hanssen, L. L. P., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24402-3 · Cited by 53 · see citing works
Self-citationHan, W., Qiu, H.-Y., Sun, S., Fu, Z.-C., Wang, G., Qian, X., Wang, L., Zhai, X., Jia, W. P., Wang, Y., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.10.007 · Cited by 51 · see citing works
Reid, X. J., Low, J. K. K., & Mackay, J. P. (2022) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2022.06.002 · Cited by 52 · see citing works
Lux, C. T., Pattabhi, S., Berger, M. P., Nourigat, C., Flowers, D. A., Nègre, O., Humbert, O., Yang, J., Lee, C., Jacoby, K., et al. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.12.008 · Cited by 50 · see citing works
Evolution of hemoglobin loci and their regulatory elements
Philipsen, S., & Hardison, R. C. (2018) · Blood Cells, Molecules, and Diseases · doi:10.1016/j.bcmd.2017.08.001 · Cited by 51 · see citing works
“The essential role of repressor proteins in orchestrating the switch from embryonic/fetal to adult globin gene expression has now been firmly established with the identification of a regulatory circuit involving MYB [96], KLF1 [97, 98], BCL11A [99] and LRF (also called Pokemon or ZBTB7A) [100].”
Takase, S., Hiroyama, T., Shirai, F., Maemoto, Y., Nakata, A., Arata, M., Matsuoka, S., Sonoda, T., Niwa, H., Sato, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35404-0 · Cited by 50 · see citing works
Self-citationFetal hemoglobin in sickle cell anemia: The Arab‐Indian haplotype and new therapeutic agents
Habara, A. H., Mohammed, E. S. E., & Steinberg, M. H. (2017) · American Journal of Hematology · doi:10.1002/ajh.24872 · Cited by 51 · see citing works
“Leukemia/lymphoma-related factor (LRF), encoded by ZBTB7A, another zinc finger transcription factor, is another important repressor of HBG transcription.(18) Following ZBTB7A knockout in the HUDEP-2 human erythroid cell line that expresses adult HbA on terminal differentiation, HbF levels increased to 70%.”
BackgroundMethodInfluentialVinjamur, D. S., & Bauer, D. E. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7428-3_17 · Cited by 48 · see citing works
Self-citationCRISPR-Cas9 to induce fetal hemoglobin for the treatment of sickle cell disease
Demirci, S., Leonard, A. K., Essawi, K., & Tisdale, J. F. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.09.010 · Cited by 50 · see citing works
“CRISPR-Cas9-mediated editing of the binding region induced robust g-globin expression in both progenitor cells and an immortalized human erythroid cell line (HUDEP-2).(24,27) In addition to the BCL11A binding region, disruption of the ZBTB7A (also known as LRF) binding site ( 200 region, Figure 1) provided substantial…”
BackgroundFetal hemoglobin regulation in β-thalassemia: heterogeneity, modifiers and therapeutic approaches
Sripichai, O., & Fucharoen, S. (2016) · Expert Review of Hematology · doi:10.1080/17474086.2016.1255142 · Cited by 48 · see citing works
“Recently, the zinc finger and BTB domain containing 7A (ZBTB7A/LRF/Pokemon) was identified as a potent silencer [56].”
BackgroundSchoonenberg, V. A. C., Cole, M. A., Yao, Q., Macias-Treviño, C., Sher, F., Schupp, P. G., Canver, M. C., Maeda, T., Pinello, L., & Bauer, D. E. (2018) · Genome Biology · doi:10.1186/s13059-018-1563-5 · Cited by 42 · see citing works
Self-citationEnhanced HbF reactivation by multiplex mutagenesis of thalassemic CD34+ cells in vitro and in vivo
Psatha, N., Georgakopoulou, A., Li, C., Nandakumar, V., Georgolopoulos, G., Acosta, R., Paschoudi, K., Nelson, J. S., Chee, D. R., Athanasiadou, A., et al. (2021) · Blood · doi:10.1182/blood.2020010020 · Cited by 48 · see citing works
Self-citationThe multi-faceted functioning portrait of LRF/ZBTB7A
Constantinou, C., Σπέλλα, Μ., Chondrou, V., Patrinos, G. P., Papachatzopoulou, A., & Sgourou, A. (2019) · Human Genomics · doi:10.1186/s40246-019-0252-0 · Cited by 49 · see citing works
SIRT1 activates the expression of fetal hemoglobin genes
Dai, Y., Chen, T., Ijaz, H., Cho, E. H., & Steinberg, M. H. (2017) · American Journal of Hematology · doi:10.1002/ajh.24879 · Cited by 46 · see citing works
Hemoglobin genetics: recent contributions of GWAS and gene editing
Smith, E. C., & Orkin, S. H. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw170 · Cited by 45 · see citing works
“Quite recently, another potent silencer, called leukemia/ lymphoma-related factor (LRF)/Pokemon/ZBTB7A, was identified through focused studies of its role in erythroid differentiation by Maeda and coworkers (26).”
BackgroundSelf-citationChen, D., Zuo, Y., Zhang, X., Ye, Y., Bao, X., Huang, H., Tepakhan, W., Wang, L., Ju, J., Chen, G., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.05.012 · Cited by 45 · see citing works
Morrison, T. A., Wilcox, I., Luo, H., Farrell, J. J., Kurita, R., Nakamura, Y., Murphy, G. J., Cui, S., Steinberg, M. H., & Chui, D. H. K. (2017) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2017.11.003 · Cited by 44 · see citing works
“HUDEP-2 cells, which do not have the 3-bp deletion at rs66650371 (data not shown) and synthesize almost exclusively HBB have been used to study the regulation of HBG expression [6,13,14].”
BackgroundMethodSelf-citationSwitching from fetal to adult hemoglobin
Wang, X., & Thein, S. L. (2018) · Nature Genetics · doi:10.1038/s41588-018-0094-z · Cited by 44 · see citing works
Self-citationPittol, J. M. R., Oruba, A., Mittler, G., Saccani, S., & van Essen, D. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2004526 · Cited by 43 · see citing works
Sickle cell disease: progress towards combination drug therapy
Pace, B. S., Starlard‐Davenport, A., & Kutlar, A. (2021) · British Journal of Haematology · doi:10.1111/bjh.17312 · Cited by 43 · see citing works
“Correction of the HBB or high-level pancellular HbF expression could be curative, therefore we will discuss gene therapy drugs currently in clinical trials to achieve both approaches.(112,113) In 2014, the first SCA patient was successfully treated with gene therapy as part of a phase 1/2 clinical trial (HGB-205).”
MethodAntoniani, C., Romano, O., & Miccio, A. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0192 · Cited by 43 · see citing works
Gene Therapy and Gene Editing for β-Thalassemia
Christakopoulos, G. E., Telange, R., Yen, J. S., & Weiss, M. J. (2023) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.12.012 · Cited by 42 · see citing works
Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells
Qin, K., Huang, P., Feng, R., Keller, C. A., Peslak, S. A., Khandros, E., Saari, M. S., Lan, X., Mayuranathan, T., Doerfler, P. A., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01076-1 · Cited by 42 · see citing works
GATA Factor-Mediated Gene Regulation in Human Erythropoiesis
Romano, O., Petiti, L., Félix, T., Meneghini, V., Portafax, M., Antoniani, C., Amendola, M., Bicciato, S., Peano, C., & Miccio, A. (2020) · iScience · doi:10.1016/j.isci.2020.101018 · Cited by 40 · see citing works
“Moreover, undifferentiated HUDEP-2 cells present accessible chromatin regions mapping to the E-Prog-specific KIT enhancers (Figure S8C), suggesting that these regulatory elements are active in this cell line (Masuda et al., 2016).”
BackgroundShang, S., Li, X., Azzo, A., Truong, T., Dozmorov, M. G., Lyons, C. E., Manna, A. K., Williams, D. C., & Ginder, G. D. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2302254120 · Cited by 40 · see citing works
“Previous studies from our lab and others showed that knockout of either BCL11A or MBD2 in HUDEP2 cells and knockdown of either in CD34 cells result in very similar levels of transcriptional activation of the HBG genes (1, 3, 8, 10), further supporting the concept that these two factors act in conjunction to enforce si…”
Khandros, E., Huang, P., Peslak, S. A., Sharma, M., Abdulmalik, O., Giardine, B. M., Zhang, Z., Keller, C. A., Hardison, R. C., & Blobel, G. A. (2020) · Blood · doi:10.1182/blood.2020005058 · Cited by 40 · see citing works
Mehta, S., Buyanbat, A., Yan, K., Karayel, Ö., Goldman, S. R., Seruggia, D., Zhang, K., Fujiwara, Y., Donovan, K. A., Zhu, Q., et al. (2022) · Cell chemical biology · doi:10.1016/j.chembiol.2022.06.007 · Cited by 39 · see citing works
Self-citationHematopoietic Stem Cell-Targeted Gene-Addition and Gene-Editing Strategies for β-hemoglobinopathies
Drysdale, C. M., Nassehi, T., Gamer, J., Yapundich, M., Tisdale, J. F., & Uchida, N. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.01.001 · Cited by 39 · see citing works
Pharmacological and molecular approaches for the treatment of β‐hemoglobin disorders
Lohani, N., Bhargava, N., Munshi, A., & Ramalingam, S. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26292 · Cited by 38 · see citing works
“Multiple research groups have used genome wide association studies (GWAS) to find associations between common genetic modifiers of β-hemoglobin disorders and alterations in HbF levels (Masuda et al., 2016; Xu et al., 2011) Table 1.”
BackgroundCRISPR/Cas9-based gene-editing technology for sickle cell disease
Ma, L., Yang, S., Peng, Q., Zhang, J., & Zhang, J. (2023) · Gene · doi:10.1016/j.gene.2023.147480 · Cited by 44 · see citing works
Revolutionising healing: Gene Editing's breakthrough against sickle cell disease
Dimitrievska, M., Bansal, D., Vitale, M., Strouboulis, J., Miccio, A., Nicolaides, K. H., Hoss, S. E., Shangaris, P., & Jackow, J. (2024) · Blood Reviews · doi:10.1016/j.blre.2024.101185 · Cited by 39 · see citing works
Soni, S. (2020) · American Journal of Hematology · doi:10.1002/ajh.25909 · Cited by 37 · see citing works
Non-Transfusion-Dependent Thalassemia: A Panoramic Review
Shash, H. A. (2022) · Medicina · doi:10.3390/medicina58101496 · Cited by 36 · see citing works
“One of the potential targets for gene editing is the erythroid-specific transcription factor BCL11A, which normally represses the expression of γ-globin [88,89,91].”
BackgroundStructural basis for human ZBTB7A action at the fetal globin promoter
Yang, Y., Ren, R., Ly, L. C., Horton, J. R., Li, F., Quinlan, K. G. R., Crossley, M., Shi, Y., & Cheng, X. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109759 · Cited by 36 · see citing works
“Our results firmly establish ZBTB7A/LRF as a key molecular regulator of fetal globin expression and inform genome-editing strategies that inhibit repressor binding and boost fetal globin expression to treat hemoglobinopathies.”
BackgroundResultInfluentialSelf-citationElevating fetal hemoglobin: recently discovered regulators and mechanisms
Khandros, E., & Blobel, G. A. (2024) · Blood · doi:10.1182/blood.2023022190 · Cited by 32 · see citing works
The E3 ligase adaptor molecule SPOP regulates fetal hemoglobin levels in adult erythroid cells
Lan, X., Khandros, E., Huang, P., Peslak, S. A., Bhardwaj, S. K., Grevet, J. D., Abdulmalik, O. Y., Wang, H., Keller, C. A., Giardine, B. M., et al. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019032318 · Cited by 33 · see citing works
Epigenetic inactivation of ERF reactivates γ-globin expression in β-thalassemia
Bao, X., Zhang, X., Wang, L., Wang, Z., Huang, J., Zhang, Q., Ye, Y., Liu, Y., Chen, D., Zuo, Y., et al. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.03.005 · Cited by 33 · see citing works
Self-citationKing, A. J., & Higgs, D. R. (2018) · Hematology · doi:10.1182/asheducation-2018.1.353 · Cited by 33 · see citing works
“356 American Society of Hematology The zinc finger transcriptional repressor LRF (also known as Pokemon, osteoclast-derived ZF, FBI-1, and ZBTB7A) is a member of the BTB/POZ-ZF family; it is known to bind directly to DNA as a homodimer and leads to transcriptional silencing via chromatin modifications.33 Recent work p…”
BackgroundInfluentialSelf-citationC2H2 proteins: Evolutionary aspects of domain architecture and diversification
Bonchuk, A. N., & Georgiev, P. G. (2024) · BioEssays · doi:10.1002/bies.202400052 · Cited by 32 · see citing works
“These include well-studied human transcription factors that function as tumor suppressors, such as ZBTB7, [105–110] ZBTB20 [111] and HIC (hypermethylated in cancer).”
Molecular Medicine: Found in Translation
Orkin, S. H. (2021) · Med · doi:10.1016/j.medj.2020.12.011 · Cited by 35 · see citing works
Self-citationA unified model of human hemoglobin switching through single-cell genome editing
Shen, Y., Verboon, J. M., Zhang, Y., Liu, N., Kim, Y. J., Marglous, S., Nandakumar, S. K., Voit, R. A., Fiorini, C., Ejaz, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25298-9 · Cited by 32 · see citing works
Self-citationBiomarker signatures of sickle cell disease severity
Du, M., Ness, S. E. V., Gordeuk, V. R., Nouraie, M. S., Nekhai, S. A., Gladwin, M. T., Steinberg, M. H., & Sebastiani, P. (2018) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2018.05.001 · Cited by 33 · see citing works
Ueda, T., Yokota, T., Okuzaki, D., Uno, Y., Mashimo, T., Kubota, Y., Sudo, T., Ishibashi, T., Shingai, Y., Doi, Y., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.11.002 · Cited by 31 · see citing works
“In addition, the globin switch to the adult-type is mediated by chromatin looping and repressive transcription factors during the maturation of fetuses (Kingsley et al., 2006; Masuda et al., 2016; Noordermeer and de Laat, 2008; Palis, 2008), which is likely promoted by ESAM-mediated inter-”
BackgroundDas, S. S., Das, S., Byram, P. K., Rahaman, M., Dolai, T. K., Chatterjee, A., & Chakravorty, N. (2020) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2020.102523 · Cited by 31 · see citing works
Genetic therapies for the first molecular disease
Doerfler, P. A., Sharma, A., Porter, J. S., Zheng, Y., Tisdale, J. F., & Weiss, M. J. (2021) · Journal of Clinical Investigation · doi:10.1172/jci146394 · Cited by 29 · see citing works
- 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 · 2014: 1
- 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 › 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
- 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
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