ArticleNature genetics2021
Activation of γ-globin gene expression by GATA1 and NF-Y in hereditary persistence of fetal hemoglobin.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 50 citations in OpenAlex.
- Global genetic modifiers of fetal hemoglobin in sickle cell disease: Systematic review and meta-analysis.iScience · 2026Article
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- UCA1 lncRNA regulates γ-globin expression by modulating the miR-148b/BCL11A axis.Life science alliance · 2026Article
- BRANCHED1 acts as a rheostat of Nuclear Factor Y-dependent epigenetic regulation in axillary bud development.Nature communications · 2026Article
- New Gene Therapy Strategy for β-Thalassemia.Stem cell reviews and reports · 2026Review
- Genetic polymorphism of SNPs rs9399137 and rs4895441in HBS1L-MYB and SNP rs766432 in BCL11A among β-thalassemia Egyptian patients.BMC genomic data · 2026Article
- Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026Review
- Single-cell transcriptomics reveals heterocellular γ-globin gene expression in Aγδβ-thalassemia.Blood advances · 2026Article
- Stage-specific TRIM10 expression regulates erythroid maturation.EMBO reports · 2025Article
- Advances in the characterization of in vitro-generated red blood cells: from biophysical properties to functional applications.Stem cell research & therapy · 2025Review
- Selective AMPKβ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway.Science advances · 2025Article
- Mechanisms of Globin Gene Regulation in Mammals.Annual review of genetics · 2025Review
- Transcriptomics and proteomics reveals the potential mechanisms of hydroquinone-inhibited erythroid differentiation in K562 cells.Toxicology research · 2025Article
- Removal of promoter CpG methylation by epigenome editing reverses HBG silencing.Nature communications · 2025Article
- Dissecting the epigenetic regulation of the fetal hemoglobin genes to unravel a novel therapeutic approach for β-hemoglobinopathies.Nucleic acids research · 2025Article
- Orphan Nuclear Receptors TR2 and TR4 in Erythropoiesis: From Mechanisms to Therapies.Biomolecules · 2025Review
- Decoding HbF reactivation by hydroxyurea in hemoglobinopathy patients through microRNA signatures.Annals of hematology · 2025Article
- Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.Cell stem cell · 2025Article
- The role(s) of NF-Y in development and differentiation.Cell death and differentiation · 2025Review
- Genetic Modifiers of Hemoglobin Expression from a Clinical Perspective in Hemoglobinopathy Patients with Beta Thalassemia and Sickle Cell Disease.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Hereditary persistence of fetal hemoglobin (HPFH) ameliorates β-hemoglobinopathies by inhibiting the developmental switch from γ-globin (HBG1/HBG2) to β-globin (HBB) gene expression. Some forms of HPFH are associated with γ-globin promoter variants that either disrupt binding motifs for transcriptional repressors or create new motifs for transcriptional activators. How these variants sustain γ-globin gene expression postnatally remains undefined. We mapped γ-globin promoter sequences functionally in erythroid cells harboring different HPFH variants. Those that disrupt a BCL11A repressor binding element induce γ-globin expression by facilitating the recruitment of nuclear transcription factor Y (NF-Y) to a nearby proximal CCAAT box and GATA1 to an upstream motif. The proximal CCAAT element becomes dispensable for HPFH variants that generate new binding motifs for activators NF-Y or KLF1, but GATA1 recruitment remains essential. Our findings define distinct mechanisms through which transcription factors and their cis-regulatory elements activate γ-globin expression in different forms of HPFH, some of which are being recreated by therapeutic genome editing.
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Registered trials
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.