ArticleBlood2010
Identification of a PRMT5-dependent repressor complex linked to silencing of human fetal globin gene expression.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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.
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
62 citing papers in PubMed, 91 citations in OpenAlex.
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- PCK2-Mediated PQBP1 Lactylation Promotes Asthmatic Inflammation through PRMT5 Inhibition.Research (Washington, D.C.) · 2026Article
- Review
- CLNS1A regulates genome stability and cell cycle progression to control CD4 T cell function and autoimmunity.Science immunology · 2025Article
- The Discovery of Selective Protein Arginine Methyltransferase 5 Inhibitors in the Management of β-Thalassemia through Computational Methods.Molecules (Basel, Switzerland) · 2024Article
- MBD2a-NuRD binds to the methylated γ-globin gene promoter and uniquely forms a complex required for silencing of HbF expression.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- Histone 4 lysine 20 tri-methylation: a key epigenetic regulator in chromatin structure and disease.Frontiers in genetics · 2023Review
- Posttranslational modifications in pathogenesis of PCOS.Frontiers in endocrinology · 2022Review
- Epigenetic Regulation of Fanconi Anemia Genes Implicates PRMT5 Blockage as a Strategy for Tumor Chemosensitization.Molecular cancer research : MCR · 2021Article
- Exploring epigenetic and microRNA approaches for γ-globin gene regulation.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Transcriptional silencing of fetal hemoglobin expression by NonO.Nucleic acids research · 2021Article
- Epigenetic activities in erythroid cell gene regulation.Seminars in hematology · 2021Article
- Recent Approaches for Manipulating Globin Gene Expression in Treating Hemoglobinopathies.Frontiers in genome editing · 2021Review
- Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin.ChemMedChem · 2020Review
- Small molecule therapeutics to treat the β-globinopathies.Current opinion in hematology · 2020Review
- Islet-specific Prmt5 excision leads to reduced insulin expression and glucose intolerance in mice.The Journal of endocrinology · 2020Article
- Targeting sickle cell disease root-cause pathophysiology with small molecules.Haematologica · 2019Review
- PRMT5 Associates With the FOXP3 Homomer and When Disabled Enhances Targeted p185Frontiers in immunology · 2019Article
- Mechanisms and Inhibitors of Histone Arginine Methylation.Chemical record (New York, N.Y.) · 2018Review
2 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
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Defining the molecular mechanisms underpinning fetal (gamma) globin gene silencing may provide strategies for reactivation of gamma-gene expression, a major therapeutic objective in patients with beta-thalassemia and sickle cell disease (SCD). We have previously demonstrated that symmetric methylation of histone H4 Arginine 3 (H4R3me2s) by the protein arginine methyltransferase PRMT5 is required for recruitment of the DNA methyltransferase DNMT3A to the gamma-promoter, and subsequent DNA methylation and gene silencing. Here we show in an erythroid cell line, and in primary adult erythroid progenitors that PRMT5 induces additional repressive epigenetic marks at the gamma-promoter through the assembly of a multiprotein repressor complex containing the histone modifying enzymes SUV4-20h1, casein kinase 2alpha (CK2alpha), and components of the nucleosome remodeling and histone deacetylation complex. Expression of a mutant form of PRMT5 lacking methyltransferase activity or shRNA-mediated knockdown of SUV4-20h1 resulted in loss of complex binding to the gamma-promoter, reversal of both histone and DNA repressive epigenetic marks, and increased gamma-gene expression. The repressive H4K20me3 mark induced by SUV4-20h1 is enriched on the gamma-promoter in erythroid progenitors from adult bone marrow compared with cord blood, suggesting developmental specificity. These studies define coordinated epigenetic events linked to fetal globin gene silencing, and provide potential therapeutic targets for the treatment of beta-thalassemia and SCD.
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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.