ArticleThe Journal of biological chemistry2012
De novo DNA methylation is required to restrict T helper lineage plasticity.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 81 citations in OpenAlex.
- Dnmt3a-dependent de novo DNA methylation enforces lineage commitment and preserves functionality of memory Th1 and Tfh cells.Cell reports · 2026Article
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- Clones in blood and stratified epithelial cells, and their drivers.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- Decoding the role of DNA methylation in allergic diseases: from pathogenesis to therapy.Cell & bioscience · 2024Review
- Dysregulation of epigenetic modifications in inborn errors of immunity.Epigenomics · 2024Review
- Evaluation of Clinical and Immunological Alterations Associated with ICF Syndrome.Journal of clinical immunology · 2023Article
- Clonal haematopoiesis and dysregulation of the immune system.Nature reviews. Immunology · 2023Review
- Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023Review
- Transcriptional and Epigenetic Regulation of Context-Dependent Plasticity in T-Helper Lineages.Immune network · 2023Review
- The Origin of Clonal Hematopoiesis and Its Implication in Human Diseases.Advances in experimental medicine and biology · 2023Review
- The impact of epigenetic modifications on allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2023Review
- Inhibiting DNA methylation and RNA editing upregulates immunogenic RNA to transform the tumor microenvironment and prolong survival in ovarian cancer.Journal for immunotherapy of cancer · 2022Article
- Article
- Donor T cell DNMT3a regulates alloreactivity in mouse models of hematopoietic stem cell transplantation.The Journal of clinical investigation · 2022Article
- Review
- Review
- Micro but mighty-Micronutrients in the epigenetic regulation of adaptive immune responses.Immunological reviews · 2022Review
- Improving CAR T-Cell Persistence.International journal of molecular sciences · 2021Review
- Single-nucleotide methylation specifically represses type I interferon in antiviral innate immunity.The Journal of experimental medicine · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Naïve CD4+ T cells are highly plastic and can differentiate into discrete lineages with unique functions during an immune response. Once differentiated, helper T cells maintain a stable transcriptional memory of their initial lineage choice and resist redifferentiation. During embryogenesis, de novo DNA methylation operates on the hypomethylated genome of the blastocyst to achieve tissue-specific patterns of gene expression. Similarly, the ifnγ promoter is hypomethylated in naïve T cells, but Th2, Th17, and iTreg differentiation is accompanied by substantial de novo DNA methylation at this locus. To determine whether de novo DNA methylation is required to restrict T helper lineage plasticity, we used mice with T cell-specific deletion of the methyltransferase DNMT3a. Induction of lineage-specific cytokines occurred normally in the absence of DNMT3a, however, DNMT3a-deficient Th2, Th17, and iTreg completely failed to methylate the ifnγ promoter. This was accompanied by an increase in the transcriptionally permissive trimethyl H3K4 mark, and a reduction in inhibitory H3K27 methylation at the ifnγ locus. Failed de novo methylation resulted in failed silencing of the ifnγ gene, as DNMT3a-deficient Th2, Th17, and iTreg cells produced significant levels of IFNγ following restimulation in the presence of IL-12. Therefore, DNMT3a-mediated DNA methylation restricts T helper plasticity by establishing an epigenetically silent chromatin structure at regulatory regions of the ifnγ gene.
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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.