ArticlePloS one2016
Chemical Inhibition of Histone Deacetylases 1 and 2 Induces Fetal Hemoglobin through Activation of GATA2.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Foetal haemoglobin inducers for reducing blood transfusion in non-transfusion-dependent beta-thalassaemias.The Cochrane database of systematic reviews · 2023Pooled it
- Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent β-thalassemia: results from Thal-Thalido study.Scientific reports · 2023Trial
- Trial
- GNL3 Orchestrates AR Transcriptional Programs to Drive Castration-Resistant Prostate Cancer and Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Roxadustat induced fetal hemoglobin in anemic CKD patients: a dual-center real-world observational cohort study.BMC nephrology · 2026Observational
- Differential effects of HDAC inhibitors in the RhoCell death discovery · 2025Article
- Functional dissection of the gene regulatory mechanism underlying variation in blood CD34Scientific reports · 2025Article
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
- Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.International journal of molecular sciences · 2025Review
- Current Trends in Clinical Trials of Prodrugs.Pharmaceuticals (Basel, Switzerland) · 2025Review
- TAL1 overexpression in induced pluripotent stem cells promotes the formation of hematopoietic cell-forming complexes but inhibits enucleationFrontiers in cell and developmental biology · 2025Article
- 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
- Trps1 acts as a regulator of Sf-1 transcription and testosterone synthesis in mouse Leydig cells.Cell biology and toxicology · 2023Article
- Medicinal chemistry advances in targeting class I histone deacetylases.Exploration of targeted anti-tumor therapy · 2023Review
- Synthesis and pharmacological evaluation of pomalidomide derivatives useful for sickle cell disease treatment.Bioorganic chemistry · 2021Article
- Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2.Molecular psychiatry · 2021Article
- Epigenetic activities in erythroid cell gene regulation.Seminars in hematology · 2021Article
- Investigating the Efficacy and Safety of Thalidomide for Treating Patients WithFrontiers in pharmacology · 2021Review
- Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis.International journal of molecular sciences · 2020Review
- HRI depletion cooperates with pharmacologic inducers to elevate fetal hemoglobin and reduce sickle cell formation.Blood advances · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Therapeutic intervention aimed at reactivation of fetal hemoglobin protein (HbF) is a promising approach for ameliorating sickle cell disease (SCD) and β-thalassemia. Previous studies showed genetic knockdown of histone deacetylase (HDAC) 1 or 2 is sufficient to induce HbF. Here we show that ACY-957, a selective chemical inhibitor of HDAC1 and 2 (HDAC1/2), elicits a dose and time dependent induction of γ-globin mRNA (HBG) and HbF in cultured primary cells derived from healthy individuals and sickle cell patients. Gene expression profiling of erythroid progenitors treated with ACY-957 identified global changes in gene expression that were significantly enriched in genes previously shown to be affected by HDAC1 or 2 knockdown. These genes included GATA2, which was induced greater than 3-fold. Lentiviral overexpression of GATA2 in primary erythroid progenitors increased HBG, and reduced adult β-globin mRNA (HBB). Furthermore, knockdown of GATA2 attenuated HBG induction by ACY-957. Chromatin immunoprecipitation and sequencing (ChIP-Seq) of primary erythroid progenitors demonstrated that HDAC1 and 2 occupancy was highly correlated throughout the GATA2 locus and that HDAC1/2 inhibition led to elevated histone acetylation at well-known GATA2 autoregulatory regions. The GATA2 protein itself also showed increased binding at these regions in response to ACY-957 treatment. These data show that chemical inhibition of HDAC1/2 induces HBG and suggest that this effect is mediated, at least in part, by histone acetylation-induced activation of the GATA2 gene.
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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.