ArticleBlood2015
EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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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.
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
67 citing papers in PubMed, 104 citations in OpenAlex.
- Trial
- New Gene Therapy Strategy for β-Thalassemia.Stem cell reviews and reports · 2026Review
- Targeted protein degradation for fetal hemoglobin induction: a new paradigm in β-hemoglobinopathy therapy.Biomarker research · 2026Review
- 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
- MAZ regulates fetal hemoglobin repression by activating MYB transcription.Scientific reports · 2025Article
- 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
- A tetramer of BCL11A is required for stable protein production and fetal hemoglobin silencing.Science (New York, N.Y.) · 2024Article
- 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
- A Live-Cell Epigenome Manipulation by Photo-Stimuli-Responsive Histone Methyltransferase Inhibitor.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- 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
- C2H2 Zinc Finger Transcription Factors Associated with Hemoglobinopathies.Journal of molecular biology · 2024Review
- Article
- Discovery of Ligands for TRIM58, a Novel Tissue-Selective E3 Ligase.ACS medicinal chemistry letters · 2023Article
- Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Fetal hemoglobin (HbF, α2γ2) induction is a well-validated strategy for sickle cell disease (SCD) treatment. Using a small-molecule screen, we found that UNC0638, a selective inhibitor of EHMT1 and EHMT2 histone methyltransferases, induces γ-globin expression. EHMT1/2 catalyze mono- and dimethylation of lysine 9 on histone 3 (H3K9), raising the possibility that H3K9Me2, a repressive chromatin mark, plays a role in silencing γ-globin expression. In primary human adult erythroid cells, UNC0638 and EHMT1 or EHMT2 short hairpin RNA-mediated knockdown significantly increased γ-globin expression, HbF synthesis, and the percentage of cells expressing HbF. At effective concentrations, UNC0638 did not alter cell morphology, proliferation, or erythroid differentiation of primary human CD34(+) hematopoietic stem and progenitor cells in culture ex vivo. In murine erythroleukemia cells, UNC0638 and Ehmt2 CRISPR/Cas9-mediated knockout both led to a marked increase in expression of embryonic β-globin genes Hbb-εy and Hbb-βh1. In primary human adult erythroblasts, chromatin immunoprecipitation followed by sequencing analysis revealed that UNC0638 treatment leads to genome-wide depletion in H3K9Me2 and a concomitant increase in the activating mark H3K9Ac, which was especially pronounced at the γ-globin gene region. In RNA-sequencing analysis of erythroblasts, γ-globin genes were among the most significantly upregulated genes by UNC0638. Further increase in γ-globin expression in primary human adult erythroid cells was achieved by combining EHMT1/2 inhibition with the histone deacetylase inhibitor entinostat or hypomethylating agent decitabine. Our data provide genetic and pharmacologic evidence that EHMT1 and EHMT2 are epigenetic regulators involved in γ-globin repression and represent a novel therapeutic target for SCD.
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What OpenQuestion holds
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.