ArticleThe Journal of clinical investigation2021
Identification of direct transcriptional targets of NFATC2 that promote β cell proliferation.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- In Depth Characterization of the Promoter Proximal Proteome of Single Copy Locus FOXP2.Molecular & cellular proteomics : MCP · 2026Article
- FOXC2 represses NFAT1-dependent transcription through a DNA-facilitated protein-protein interaction.Nucleic acids research · 2026Article
- Cardiac lymphatics: functional plasticity in development, disease, and precision-targeted therapies.Basic research in cardiology · 2026Review
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Development of Potential Pharmacological Targets to Normalize Gene Expression in Islets of Type 2 Diabetic Patients.Current medicinal chemistry · 2026Article
- Mechanisms inducing differentiation of adult islet progenitor-like cells into functional islet-like organoids.Frontiers in transplantation · 2026Article
- Porphyromonas gingivalis extracellular vesicles promotes tumor metastasis in esophageal squamous cell carcinoma by inducing PRKACB/JNK/ NFATC2 axis.Journal of nanobiotechnology · 2025Article
- A mechanism-informed deep neural network enables prioritization of regulators that drive cell state transitions.Nature communications · 2025Article
- Dual role of neuroplastin in pancreatic β cells: Regulating insulin secretion and promoting islet inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Genetic deficiency of the transcription factor NFAT1 confers protection against fibrogenic responses independent of immune influx.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells.Nature communications · 2023Article
- Review
- CaBiomedicines · 2023Review
- The metabolic nature of inflammatory bowel diseases.Nature reviews. Gastroenterology & hepatology · 2022Review
- Disrupting the DREAM complex enables proliferation of adult human pancreatic β cells.The Journal of clinical investigation · 2022Article
- Article
- [Metformin and lipopolysaccharide regulate transcription ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Dynamic changes in β-cell [CaMolecular metabolism · 2022Article
- FOXP family DNA methylation correlates with immune infiltration and prognostic value in NSCLC.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 1 country.
Funding
Abstract
The transcription factor NFATC2 induces β cell proliferation in mouse and human islets. However, the genomic targets that mediate these effects have not been identified. We expressed active forms of Nfatc2 and Nfatc1 in human islets. By integrating changes in gene expression with genomic binding sites for NFATC2, we identified approximately 2200 transcriptional targets of NFATC2. Genes induced by NFATC2 were enriched for transcripts that regulate the cell cycle and for DNA motifs associated with the transcription factor FOXP. Islets from an endocrine-specific Foxp1, Foxp2, and Foxp4 triple-knockout mouse were less responsive to NFATC2-induced β cell proliferation, suggesting the FOXP family works to regulate β cell proliferation in concert with NFATC2. NFATC2 induced β cell proliferation in both mouse and human islets, whereas NFATC1 did so only in human islets. Exploiting this species difference, we identified approximately 250 direct transcriptional targets of NFAT in human islets. This gene set enriches for cell cycle-associated transcripts and includes Nr4a1. Deletion of Nr4a1 reduced the capacity of NFATC2 to induce β cell proliferation, suggesting that much of the effect of NFATC2 occurs through its induction of Nr4a1. Integration of noncoding RNA expression, chromatin accessibility, and NFATC2 binding sites enabled us to identify NFATC2-dependent enhancer loci that mediate β cell proliferation.
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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.