ArticleEuropean journal of haematology2009
Erythroid Kruppel-like factor (EKLF) is recruited to the gamma-globin gene promoter as a co-activator and is required for gamma-globin gene induction by short-chain fatty acid derivatives.
Article in European journal of haematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04432623 (A Phase 1b Sequential Open Label Dose-Ranging Study of Safety, Pharmacokinetics, and Preliminary Activity of Benserazide in Subjects With Beta Thalassemia Intermedia and Sickle Cell Disease), which is not on this map. Cited by 17 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1b Sequential Open Label Dose-Ranging Study of Safety, Pharmacokinetics, and Preliminary Activity of Benserazide in Subjects With Beta Thalassemia Intermedia and Sickle Cell Disease
Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- A randomized phase I/II trial of HQK-1001, an oral fetal globin gene inducer, in β-thalassaemia intermedia and HbE/β-thalassaemia.British journal of haematology · 2013Trial
- A phase 1/2 trial of HQK-1001, an oral fetal globin inducer, in sickle cell disease.American journal of hematology · 2012Trial
- Highly discriminative globin gene activation by the noncanonical BAF chromatin remodeling complex.Blood · 2026Article
- Genetic Engineering in Hematopoietic Stem Cells for β-Hemoglobinopathies Treatment: Advances, Challenges, and Clinical Translation.International journal of hematology-oncology and stem cell research · 2025Review
- Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications.International journal of molecular sciences · 2024Review
- Gamma reactivation using the spongy effect of KLF1-binding site sequence: an approach in gene therapy for beta-thalassemia.Iranian journal of basic medical sciences · 2016Article
- Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms.Blood cells, molecules & diseases · 2016Article
- Induction of functional Brm protein from Brm knockout mice.Oncoscience · 2015Article
- Article
- Regulation of Gγ-globin gene by ATF2 and its associated proteins through the cAMP-response element.PloS one · 2013Article
- EKLF/KLF1, a tissue-restricted integrator of transcriptional control, chromatin remodeling, and lineage determination.Molecular and cellular biology · 2013Review
- Butyrate histone deacetylase inhibitors.BioResearch open access · 2012Article
- Functional interactions between erythroid Krüppel-like factor (EKLF/KLF1) and protein phosphatase PPM1B/PP2Cβ.The Journal of biological chemistry · 2012Article
- Article
- Review
- Novel therapeutic candidates, identified by molecular modeling, induce γ-globin gene expression in vivo.Blood cells, molecules & diseases · 2011Article
- Fetal globin gene inducers: novel agents and new potential.Annals of the New York Academy of Sciences · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesThe erythroid Kruppel-like factor (EKLF) is an essential transcription factor for beta-type globin gene switching, and specifically activates transcription of the adult beta-globin gene promoter. We sought to determine if EKLF is also required for activation of the gamma-globin gene by short-chain fatty acid (SCFA) derivatives, which are now entering clinical trials.
methodsThe functional and physical interaction of EKLF and co-regulatory molecules with the endogenous human globin gene promoters was studied in primary human erythroid progenitors and cell lines, using chromatin immunoprecipitation (ChIP) assays and genetic manipulation of the levels of EKLF and co-regulators. RESULTS AND
conclusionsKnockdown of EKLF prevents SCFA-induced expression of the gamma-globin promoter in a stably expressed microLCRbeta(pr)R(luc) (A)gamma(pr)F(luc) cassette, and prevents induction of the endogenous gamma-globin gene in primary human erythroid progenitors. EKLF is actively recruited to endogenous gamma-globin gene promoters after exposure of primary human erythroid progenitors, and murine hematopoietic cell lines, to SCFA derivatives. The core ATPase BRG1 subunit of the human SWI/WNF complex, a ubiquitous multimeric complex that regulates gene expression by remodeling nucleosomal structure, is also required for gamma-globin gene induction by SCFA derivatives. BRG1 is actively recruited to the endogenous gamma-globin promoter of primary human erythroid progenitors by exposure to SCFA derivatives, and this recruitment is dependent upon the presence of EKLF. These findings demonstrate that EKLF, and the co-activator BRG1, previously demonstrated to be required for definitive or adult erythropoietic patterns of globin gene expression, are co-opted by SCFA derivatives to activate the fetal globin genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.