ArticleBlood2015
Inhibition of G9a methyltransferase stimulates fetal hemoglobin production by facilitating LCR/γ-globin looping.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 93 citations in OpenAlex.
- LDB1 regulates gene expression and chromatin structure in pluripotency and lineage differentiation.Nucleic acids research · 2026Article
- Enhanced induction of fetal hemoglobin by the combination of decitabine with RN-1 in β-thalassemia/HbE erythroid progenitor cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- A Novel Aberrant HbF Peak with Electrophoretic Shift in A1c of a Patient with Chronic Lymphocytic Leukemia (CLL) Was Reversible to Give Interpretable Results.Biomedicines · 2026Article
- Histone modifications in the regulation of erythropoiesis.Annals of medicine · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- BRD4 acts as a transcriptional repressor of RhoB to inhibit terminal erythropoiesis.Journal of hematology & oncology · 2025Article
- Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.International journal of molecular sciences · 2025Review
- Orphan Nuclear Receptors TR2 and TR4 in Erythropoiesis: From Mechanisms to Therapies.Biomolecules · 2025Review
- The induction effect of hydroxyurea and metformin on fetal globin in the K562 cell line.Molecular medicine (Cambridge, Mass.) · 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
- Review
- Newly developed oral bioavailable EHMT2 inhibitor as a potential epigenetic therapy for Prader-Willi syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- A cellular reporter system to evaluate endogenous fetal hemoglobin induction and screen for therapeutic compounds.HemaSphere · 2024Article
- The Discovery of Selective Protein Arginine Methyltransferase 5 Inhibitors in the Management of β-Thalassemia through Computational Methods.Molecules (Basel, Switzerland) · 2024Article
- Discovery of the First-in-Class G9a/GLP PROTAC Degrader.Journal of medicinal chemistry · 2024Article
- C2H2 Zinc Finger Transcription Factors Associated with Hemoglobinopathies.Journal of molecular biology · 2024Review
- Discovery of the First-in-class G9a/GLP PROTAC Degrader.bioRxiv : the preprint server for biology · 2024Article
- Article
- Review
- A specific G9a inhibitor unveils BGLT3 lncRNA as a universal mediator of chemically induced fetal globin gene expression.Nature communications · 2023Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Induction of fetal hemoglobin (HbF) production in adult erythrocytes can reduce the severity of sickle cell disease and β-thalassemia. Transcription of β-globin genes is regulated by the distant locus control region (LCR), which is brought into direct gene contact by the LDB1/GATA-1/TAL1/LMO2-containing complex. Inhibition of G9a H3K9 methyltransferase by the chemical compound UNC0638 activates fetal and represses adult β-globin gene expression in adult human hematopoietic precursor cells, but the underlying mechanisms are unclear. Here we studied UNC0638 effects on β-globin gene expression using ex vivo differentiation of CD34(+) erythroid progenitor cells from peripheral blood of healthy adult donors. UNC0638 inhibition of G9a caused dosed accumulation of HbF up to 30% of total hemoglobin in differentiated cells. Elevation of HbF was associated with significant activation of fetal γ-globin and repression of adult β-globin transcription. Changes in gene expression were associated with widespread loss of H3K9me2 in the locus and gain of LDB1 complex occupancy at the γ-globin promoters as well as de novo formation of LCR/γ-globin contacts. Our findings demonstrate that G9a establishes epigenetic conditions preventing activation of γ-globin genes during differentiation of adult erythroid progenitor cells. In this view, manipulation of G9a represents a promising epigenetic approach for treatment of β-hemoglobinopathies.
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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.