ArticleMolecular and cellular biology2008
A T-to-G transversion at nucleotide -567 upstream of HBG2 in a GATA-1 binding motif is associated with elevated hemoglobin F.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- The Molecular Pathology of Non-Malignant Haematological Disease.British journal of biomedical science · 2026Review
- Beyond transfusions and transplants: genomic innovations rewriting the narrative of thalassemia.Annals of hematology · 2025Review
- Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factors.Scientific reports · 2023Article
- Optimized minimal genome-wide human sgRNA library.Scientific reports · 2023Article
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- Transcriptional silencing of fetal hemoglobin expression by NonO.Nucleic acids research · 2021Article
- Fetal Hemoglobin in Sickle Hemoglobinopathies: High HbF Genotypes and Phenotypes.Journal of clinical medicine · 2020Review
- Small molecule therapeutics to treat the β-globinopathies.Current opinion in hematology · 2020Review
- Engineering Globin Gene Expression.Molecular therapy. Methods & clinical development · 2019Review
- Fetal hemoglobin induction in sickle erythroid progenitors using a synthetic zinc finger DNA-binding domain.Haematologica · 2018Article
- Synergistic effect of two β globin gene cluster mutations leading to the hereditary persistence of fetal hemoglobin (HPFH) phenotype.Molecular biology reports · 2017Article
- Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- An international effort to cure a global health problem: A report on the 19th Hemoglobin Switching Conference.Experimental hematology · 2015Review
- Screening of Transcription Factors Involved in Fetal Hemoglobin Regulation Using Phylogenetic Footprinting.Evolutionary bioinformatics online · 2015Article
- Fetal globin gene repressors as drug targets for molecular therapies to treat the β-globinopathies.Molecular and cellular biology · 2014Review
- Mi2β is required for γ-globin gene silencing: temporal assembly of a GATA-1-FOG-1-Mi2 repressor complex in β-YAC transgenic mice.PLoS genetics · 2012Article
- A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression.Blood · 2011Article
- Article
- Eos negatively regulates human γ-globin gene transcription during erythroid differentiation.PloS one · 2011Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Increased fetal hemoglobin (Hb F; alpha(2)gamma(2)) production in adults can ameliorate the clinical severity of sickle cell disease and beta-thalassemia major. Thus, understanding the regulation of gamma-globin gene expression and its silencing in adults has potential therapeutic implications. We studied a father and son in an Iranian-American family who had elevated Hb F levels and found a novel T-to-G transversion at nucleotide (nt) -567 of the HBG2 promoter. This mutation alters a GATA-1 binding motif to a GAGA sequence located within a previously identified silencing element. DNA-protein binding assays showed that the GATA motif of interest is capable of binding GATA-1 transcription factor in vitro and in vivo. Truncation analyses of the HBG2 promoter linked to a luciferase reporter gene revealed a negative regulatory activity present between nt -675 and -526. In addition, the T-to-G mutation at the GATA motif increased the promoter activity by two- to threefold in transiently transfected erythroid cell lines. The binding motif is uniquely conserved in simian primates with a fetal pattern of gamma-globin gene expression. These results suggest that the GATA motif under study has a functional role in silencing gamma-globin gene expression in adults. The T-to-G mutation in this motif disrupts GATA-1 binding and the associated repressor complex, abolishing its silencing effect and resulting in the up-regulation of gamma-globin gene expression in adults.
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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.