ArticleThe Journal of biological chemistry2011
Histone 3 lysine 9 (H3K9) methyltransferase recruitment to the interleukin-2 (IL-2) promoter is a mechanism of suppression of IL-2 transcription by the transforming growth factor-β-Smad pathway.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Methylome profiling of SetDB1-deficient ESCs reveals coordinated epigenetic cross-talk during pluripotency.Stem cell reports · 2026Article
- The Many Faces of SetDB1.Epigenomes · 2026Review
- Targeting SETDB1 in cancer and immune regulation: Potential therapeutic strategies in cancer.The Kaohsiung journal of medical sciences · 2025Review
- Oridonin Preserves Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates Choroidal Neovascularization.Investigative ophthalmology & visual science · 2025Article
- Double, double toil and trouble: transforming growth factor beta (TGF-β) in HIV infection.Frontiers in immunology · 2025Review
- SETDB1 modulates the TGFβ response in Duchenne muscular dystrophy myotubes.Science advances · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Review
- The role of histone methylase and demethylase in antitumor immunity: A new direction for immunotherapy.Frontiers in immunology · 2022Review
- Resident Immune Cells of the Liver in the Tumor Microenvironment.Frontiers in oncology · 2022Review
- Epigenetic modulation of antitumor immunity for improved cancer immunotherapy.Molecular cancer · 2021Review
- Structure, Activity and Function of the SETDB1 Protein Methyltransferase.Life (Basel, Switzerland) · 2021Review
- Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis.International journal of molecular sciences · 2021Review
- Global Histone H3 Lysine 4 Trimethylation (H3K4me3) Landscape Changes in Response to TGFβ.Epigenetics insights · 2021Article
- Crosstalk Between Inflammatory Signaling and Methylation in Cancer.Frontiers in cell and developmental biology · 2021Review
- Epigenetic regulation of epithelial-mesenchymal transition: focusing on hypoxia and TGF-β signaling.Journal of biomedical science · 2020Review
- Regulation of T cell differentiation and function by epigenetic modification enzymes.Seminars in immunopathology · 2019Review
- Specificity, versatility, and control of TGF-β family signaling.Science signaling · 2019Review
- Recombinant Pregnancy-Specific Glycoprotein 1 Has a Protective Role in a Murine Model of Acute Graft-versus-Host Disease.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019Article
- Infection with enteric pathogens Salmonella typhimurium and Citrobacter rodentium modulate TGF-beta/Smad signaling pathways in the intestine.Gut microbes · 2018Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suppression of IL-2 βproduction from T cells is an important process for the immune regulation by TGF-β. However, the mechanism by which this suppression occurs remains to be established. Here, we demonstrate that Smad2 and Smad3, two major TGF-β-downstream transcription factors, are redundantly essential for TGF-β-mediated suppression of IL-2 production in CD4(+) T cells using Smad2- and Smad3-deficient T cells. Both Smad2 and Smad3 were recruited into the proximal region of the IL-2 promoter in response to TGF-β. We then investigated the histone methylation status of the IL-2 promoter. Although both histone H3 lysine 9 (H3K9) and H3K27 trimethylation have been implicated in gene silencing, only H3K9 trimethylation was increased in the proximal region of the IL-2 promoter in a Smad2/3-dependent manner, whereas H3K27 trimethylation was not. The H3K9 methyltransferases Setdb1 and Suv39h1 bound to Smad3 and suppressed IL-2 promoter activity in collaboration with Smad3. Overexpression of Suv39h1 in 68-41 T cells strongly inhibited IL-2 production in response to T cell receptor stimulation irrespective of the presence or absence of TGF-β, whereas Setdb1 overexpression only slightly suppressed IL-2 production. Silencing of Suv39h1 by shRNA reverted the suppressive effect of TGF-β on IL-2 production. Furthermore, TGF-β induced Suv39h1 recruitment to the proximal region of the IL-2 promoter in wild type primary T cells; however, this was not observed in Smad2(-/-)Smad3(+/-) T cells. Thus, we propose that Smads recruit H3K9 methyltransferases Suv39h1 to the IL-2 promoter, thereby inducing suppressive histone methylation and inhibiting T cell receptor-mediated IL-2 transcription.
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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.