ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Opposing roles of STAT4 and Dnmt3a in Th1 gene regulation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
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- A proposed convergent molecular chain linking senescence, cancer, and chronic infection to a correctable failure of dendritic cell instruction.Frontiers in immunology · 2026Review
- A View of Myeloid Transformation through the Hallmarks of Cancer.Blood cancer discovery · 2024Review
- Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases.Journal of pharmaceutical analysis · 2024Review
- Intrinsic sexual dimorphism in the placenta determines the differential response to benzene exposure.iScience · 2023Article
- Clonal hematopoiesis, somatic mosaicism, and age-associated disease.Physiological reviews · 2023Review
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- JMJD family proteins in cancer and inflammation.Signal transduction and targeted therapy · 2022Review
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- Somatic Mutations of Hematopoietic Cells Are an Additional Mechanism of Body Aging, Conducive to Comorbidity and Increasing Chronification of Inflammation.Biomedicines · 2022Review
- Histone 3 Lysine 27 Trimethylation Signature in Breast Cancer.International journal of molecular sciences · 2021Review
- A feedback loop: Interactions between Inflammatory Signals and Clonal Hematopoiesis in Cardiovascular Disease.Molecular biology reports · 2021Review
- DNA Methylation in T-Cell Acute Lymphoblastic Leukemia: In Search for Clinical and Biological Meaning.International journal of molecular sciences · 2021Review
- Jumonji domain containing-3 (JMJD3) inhibition attenuates IL-1β-induced chondrocytes damage in vitro and protects osteoarthritis cartilage in vivo.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Article
- Cardiovascular Disease, Aging, and Clonal Hematopoiesis.Annual review of pathology · 2020Review
- AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation.The Journal of experimental medicine · 2020Article
- IL-12 Signaling Contributes to the Reprogramming of Neonatal CD8Frontiers in immunology · 2020Article
- Upregulation of H3K27 Demethylase KDM6 During Respiratory Syncytial Virus Infection Enhances Proinflammatory Responses and Immunopathology.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The STAT transcription factor STAT4 is a critical regulator of Th1 differentiation and inflammatory disease. Yet, how STAT4 regulates gene expression is still unclear. In this report, we define a STAT4-dependent sequence of events including histone H3 lysine 4 methylation, Jmjd3 association with STAT4 target loci, and a Jmjd3-dependent decrease in histone H3 lysine 27 trimethylation and DNA methyltransferase (Dnmt) 3a association with STAT4 target loci. Dnmt3a has an obligate role in repressing Th1 gene expression, and in Th1 cultures deficient in both STAT4 and Dnmt3a, there is recovery in the expression of a subset of Th1 genes that is sufficient to increase IFN-γ production. Moreover, although STAT4-deficient mice are protected from the development of experimental autoimmune encephalomyelitis, mice deficient in STAT4 and conditionally deficient in Dnmt3a in T cells develop paralysis. Th1 genes that are derepressed in the absence of Dnmt3a have greater induction after the ectopic expression of the Th1-associated transcription factors T-bet and Hlx1. Together, these data demonstrate that STAT4 and Dnmt3a play opposing roles in regulating Th1 gene expression, and that one mechanism for STAT4-dependent gene programming is in establishing a derepressed genetic state susceptible to transactivation by additional fate-determining transcription factors.
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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.