ArticleMolecular and cellular biology2002
Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1, BETA2, and E47.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 180 citations in OpenAlex.
- The role of epigenetic signatures in type 2 diabetes: therapeutic advances and lifestyle interventions.Acta diabetologica · 2026Review
- Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model.International journal of molecular sciences · 2026Article
- In vivo activities of E1 elements in the insulin promoter.Communications biology · 2026Article
- A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets.Stem cell research & therapy · 2025Review
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- MODY PDX1Frontiers in endocrinology · 2025Article
- Noncanonical CDK4 signaling rescues diabetes in a mouse model by promoting β cell differentiation.The Journal of clinical investigation · 2023Article
- Human pluripotent stem cell-derived β cells: Truly immature islet β cells for type 1 diabetes therapy?World journal of stem cells · 2023Review
- PDX-1: A Promising Therapeutic Target to Reverse Diabetes.Biomolecules · 2022Review
- Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life.International journal of molecular sciences · 2022Review
- Development of a Beta Cell-Specific Expression Control Element for Recombinant Adeno-Associated Virus.Human gene therapy · 2022Article
- YY1 Regulates Glucose Homeostasis Through Controlling Insulin Transcription in Pancreatic β-Cells.Diabetes · 2022Article
- Sodium butyrate potentiates insulin secretion from rat islets at the expense of compromised expression of β cell identity genes.Cell death & disease · 2022Article
- NEUROD1 Is Required for the Early α and β Endocrine Differentiation in the Pancreas.International journal of molecular sciences · 2021Article
- CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity.Cell death & disease · 2021Article
- The Contribution of Transcriptional Coregulators in the Maintenance of β-cell Function and Identity.Endocrinology · 2021Review
- Epigenetics in β-cell adaptation and type 2 diabetes.Current opinion in pharmacology · 2020Review
- Contribution of Oxidative Stress and Impaired Biogenesis of Pancreatic β-Cells to Type 2 Diabetes.Antioxidants & redox signaling · 2019Article
- LIM-domain transcription complexes interact with ring-finger ubiquitin ligases and thereby impact islet β-cell function.The Journal of biological chemistry · 2019Article
- Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment.Cell death & disease · 2018Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic beta-cell-type-specific expression of the insulin gene requires both ubiquitous and cell-enriched activators, which are organized within the enhancer region into a network of protein-protein and protein-DNA interactions to promote transcriptional synergy. Protein-protein-mediated communication between DNA-bound activators and the RNA polymerase II transcriptional machinery is inhibited by the adenovirus E1A protein as a result of E1A's binding to the p300 coactivator. E1A disrupts signaling between the non-DNA-binding p300 protein and the basic helix-loop-helix DNA-binding factors of insulin's E-element activator (i.e., the islet-enriched BETA2 and generally distributed E47 proteins), as well as a distinct but unidentified enhancer factor. In the present report, we show that E1A binding to p300 prevents activation by insulin's beta-cell-enriched PDX-1 activator. p300 interacts directly with the N-terminal region of the PDX-1 homeodomain protein, which contains conserved amino acid sequences essential for activation. The unique combination of PDX-1, BETA2, E47, and p300 was shown to promote synergistic activation from a transfected insulin enhancer-driven reporter construct in non-beta cells, a process inhibited by E1A. In addition, E1A inhibited the level of PDX-1 and BETA2 complex formation in beta cells. These results indicate that E1A inhibits insulin gene transcription by preventing communication between the p300 coactivator and key DNA-bound activators, like PDX-1 and BETA2:E47.
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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.