ArticleNature structural & molecular biology2009
PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing.
Article in Nature structural & molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 307 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
307 citing papers in PubMed, 1 synthesis or guideline pooled it, 521 citations in OpenAlex.
- Dietary sulforaphane in cancer chemoprevention: epigenetic regulation and PRMT5-MEP50 complex inhibition-a systematic review.Frontiers in pharmacology · 2026Pooled it
- MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer.Cancer discovery · 2023Trial
- PRMT7 at the crossroads of cancer progression and therapeutic targeting (Review).Oncology reports · 2026Review
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- MTAP Deficiency as a Metabolic Vulnerability in Cancer: Implications for Synthetic Lethal Therapy.Cancer science · 2026Review
- Protein arginine methyltransferase crosstalk: decoding the synergistic-antagonistic axis in cancer therapy.Epigenetics & chromatin · 2026Review
- PRMT5 promotes psoriatic inflammation through mediating dimethylation of p65 in keratinocytes.Molecular medicine (Cambridge, Mass.) · 2026Article
- PRMT5-Cacna1d axis maintains calcium homeostasis to regulate postnatal motor development in mice.Cellular and molecular life sciences : CMLS · 2026Article
- MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario.Cancer research · 2026Review
- Dynamic regulation of histone arginine methylation in anoxic freshwater turtles.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026Article
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- A nuclear isoform of hydroxyacyl-COA dehydrogenase inhibits tumor progression in colorectal cancer.iScience · 2026Article
- PRMT5 inhibitors actively promote metastatic progression of lung adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- PCK2-Mediated PQBP1 Lactylation Promotes Asthmatic Inflammation through PRMT5 Inhibition.Research (Washington, D.C.) · 2026Article
- Enhancing CD8Biomolecules · 2025Article
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- The Role of PRMT5 in Embryonic Developmental Arrest: Insights from IVF-ET Discarded Human Embryos.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
- C6orf223 promotes colorectal cancer growth and metastasis by facilitating PRMT5-MEP50 multiprotein complex assembling.The Journal of clinical investigation · 2025Article
247 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
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Mammalian gene silencing is established through methylation of histones and DNA, although the order in which these modifications occur remains contentious. Using the human beta-globin locus as a model, we demonstrate that symmetric methylation of histone H4 arginine 3 (H4R3me2s) by the protein arginine methyltransferase PRMT5 is required for subsequent DNA methylation. H4R3me2s serves as a direct binding target for the DNA methyltransferase DNMT3A, which interacts through the ADD domain containing the PHD motif. Loss of the H4R3me2s mark through short hairpin RNA-mediated knockdown of PRMT5 leads to reduced DNMT3A binding, loss of DNA methylation and gene activation. In primary erythroid progenitors from adult bone marrow, H4R3me2s marks the inactive methylated globin genes coincident with localization of PRMT5. Our findings define DNMT3A as both a reader and a writer of repressive epigenetic marks, thereby directly linking histone and DNA methylation in gene silencing.
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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.