ArticleMolecular and cellular biology1998
p300 mediates transcriptional stimulation by the basic helix-loop-helix activators of the insulin gene.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 137 citations in OpenAlex.
- Identification and functional characterization of a novel mutation in the NEUROD1 gene in a Chinese family with maturity-onset diabetes of the young.Acta diabetologica · 2026Article
- In vivo activities of E1 elements in the insulin promoter.Communications biology · 2026Article
- Transcriptomic analysis implicates the involvement of RBM20 in Fuchs' endothelial corneal dystrophy with TCF4 repeat expansion.PloS one · 2025Article
- Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activation.Nucleic acids research · 2023Article
- From glucose sensing to exocytosis: takes from maturity onset diabetes of the young.Frontiers in endocrinology · 2023Review
- The E-Id Axis Instructs Adaptive Versus Innate Lineage Cell Fate Choice and Instructs Regulatory T Cell Differentiation.Frontiers in immunology · 2022Review
- Transcription Factor RREB1: from Target Genes towards Biological Functions.International journal of biological sciences · 2020Review
- The first case of NEUROD1-MODY reported in Latin America.Molecular genetics & genomic medicine · 2019Observational
- TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression.Genome medicine · 2019Article
- TCF-1 and HEB cooperate to establish the epigenetic and transcription profiles of CD4Nature immunology · 2018Article
- PIAS-family proteins negatively regulate Glis3 transactivation function through SUMO modification in pancreatic β cells.Heliyon · 2018Article
- SSBP3 Interacts With Islet-1 and Ldb1 to Impact Pancreatic β-Cell Target Genes.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Dynamic recruitment of functionally distinct Swi/Snf chromatin remodeling complexes modulates Pdx1 activity in islet β cells.Cell reports · 2015Article
- NFAT targets signaling molecules to gene promoters in pancreatic β-cells.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective.Cellular and molecular life sciences : CMLS · 2014Review
- CtBP and associated LSD1 are required for transcriptional activation by NeuroD1 in gastrointestinal endocrine cells.Molecular and cellular biology · 2014Article
- The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Histone deacetylases as targets for treatment of multiple diseases.Clinical science (London, England : 1979) · 2013Review
- Islet α-, β-, and δ-cell development is controlled by the Ldb1 coregulator, acting primarily with the islet-1 transcription factor.Diabetes · 2013Article
- Biochemical and phosphoproteomic analysis of the helix-loop-helix protein E47.Molecular and cellular biology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Pancreatic beta-cell-type-specific and glucose-inducible transcription of the insulin gene is mediated by the basic helix-loop-helix factors that bind to and activate expression from an E-box element within its enhancer. The E-box activator is a heteromeric complex composed of a beta-cell-enriched factor, BETA2/NeuroD, and ubiquitously distributed proteins encoded by the E2A and HEB genes. Previously, we demonstrated that the adenovirus type 5 E1A proteins repressed stimulation by the E-box activator in beta cells. In this study, our objective was to determine how E1A repressed activator function. The results indicate that E1A reduces activation by binding to and sequestering the p300 cellular coactivator protein. Thus, we show that expression of p300 in beta cells can relieve inhibition by E1A, as well as potentiate activation by the endogenous insulin E-box transcription factors. p300 stimulated activation from GAL4 (amino acids 1 to 147) fusion constructs of either BETA2/NeuroD or the E2A-encoded E47 protein. The sequences spanning the activation domains of BETA2/NeuroD (amino acids 156 to 355) and E47 (amino acids 1 to 99 and 325 to 432) were required for this response. The same region of BETA2/NeuroD was shown to be important for binding to p300 in vitro. The sequences of p300 involved in E47 and BETA2/NeuroD association resided between amino acids 1 and 1257 and 1945 and 2377, respectively. A mutation in p300 that abolished binding to BETA2/NeuroD also destroyed the ability of p300 to activate insulin E-box-directed transcription in beta cells. Our results indicate that physical and functional interactions between p300 and the E-box activator factors play an important role in insulin gene transcription.
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