ArticleBritish journal of haematology2011
Krüppel-like Factor 4 activates HBG gene expression in primary erythroid cells.
Article in British journal of haematology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Directing stem cell differentiation by chromatin state approximation.Nucleic acids research · 2026Article
- Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver.BMC biology · 2025Article
- Small-molecule α-lipoic acid targets ELK1 to balance human neutrophil and erythrocyte differentiation.Stem cell research & therapy · 2024Article
- KLF4 is an epigenetically modulated, context-dependent tumor suppressor.Frontiers in cell and developmental biology · 2024Review
- Transferrin receptor 2 (Tfr2) genetic deletion makes transfusion-independent a murine model of transfusion-dependent β-thalassemia.American journal of hematology · 2022Article
- Enhanced HbF reactivation by multiplex mutagenesis of thalassemic CD34+ cells in vitro and in vivo.Blood · 2021Article
- Downregulation of KLF4 activates embryonic and fetal globin mRNA expression in human erythroid progenitor cells.Experimental and therapeutic medicine · 2021Article
- Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism.The pharmacogenomics journal · 2018Review
- Article
- Dimethyl fumarate increases fetal hemoglobin, provides heme detoxification, and corrects anemia in sickle cell disease.JCI insight · 2017Article
- Regulation of endothelial hemoglobin alpha expression by Kruppel-like factors.Vascular medicine (London, England) · 2017Article
- Original Research: A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- Cell fate decisions in malignant hematopoiesis: leukemia phenotype is determined by distinct functional domains of the MN1 oncogene.PloS one · 2014Article
- A cell-based high-throughput screen for novel chemical inducers of fetal hemoglobin for treatment of hemoglobinopathies.PloS one · 2014Article
- Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.PloS one · 2014Article
- Comprehensive characterization of erythroid-specific enhancers in the genomic regions of human Krüppel-like factors.BMC genomics · 2013Article
- NF-Y coassociates with FOS at promoters, enhancers, repetitive elements, and inactive chromatin regions, and is stereo-positioned with growth-controlling transcription factors.Genome research · 2013Article
- Regulation of Gγ-globin gene by ATF2 and its associated proteins through the cAMP-response element.PloS one · 2013Article
- Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation.BMC genomics · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The SP1/Krüppel-like Factor (SP1/KLF) family of transcription factors plays a role in diverse cellular processes, including proliferation, differentiation and control of gene transcription. The discovery of KLF1 (EKLF), a key regulator of HBB (β-globin) gene expression, expanded our understanding of the role of KLFs in erythropoiesis. In this study, we investigated a mechanism of HBG (γ-globin) regulation by KLF4. siRNA-mediated gene silencing and enforced expression of KLF4 in K562 cells substantiated the ability of KLF4 to positively regulate endogenous HBG gene transcription. The physiological significance of this finding was confirmed in primary erythroid cells, where KLF4 knockdown at day 11 significantly attenuated HBG mRNA levels and enforced expression at day 28 stimulated the silenced HBG genes. In vitro binding characterization using the γ-CACCC and β-CACCC probes demonstrated KLF4 preferentially binds the endogenous γ-CACCC, while CREB binding protein (CREBBP) binding was not selective. Co-immunoprecipitation studies confirmed protein-protein interaction between KLF4 and CREBBP. Furthermore, sequential chromatin immunoprecipitation assays showed co-localization of both factors in the γ-CACCC region. Subsequent luciferase reporter studies demonstrated that KLF4 trans-activated HBG promoter activity and that CREBBP enforced expression resulted in gene repression. Our data supports a model of antagonistic interaction of KLF4/CREBBP trans-factors in HBG regulation.
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