ArticleProceedings of the National Academy of Sciences of the United States of America1994
Transcriptional regulation of the human insulin gene is dependent on the homeodomain protein STF1/IPF1 acting through the CT boxes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 207 citations in OpenAlex.
- Hepatic insulin synthesis increases in rat models of diabetes mellitus type 1 and 2 differently.PloS one · 2023Article
- PDX-1: A Promising Therapeutic Target to Reverse Diabetes.Biomolecules · 2022Review
- The Contribution of Transcriptional Coregulators in the Maintenance of β-cell Function and Identity.Endocrinology · 2021Review
- MicroRNA-17-92 Regulates Beta-Cell Restoration After Streptozotocin Treatment.Frontiers in endocrinology · 2020Article
- A PDX1-ATF transcriptional complex governs β cell survival during stress.Molecular metabolism · 2018Article
- Glucose regulates MafA transcription factor abundance and insulin gene expression by inhibiting AMP-activated protein kinase in pancreatic β-cells.The Journal of biological chemistry · 2018Article
- Insulin-secreting β cells require a post-genomic concept.World journal of diabetes · 2016Review
- miR-101a and miR-30b contribute to inflammatory cytokine-mediated β-cell dysfunction.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Role of pancreatic transcription factors in maintenance of mature β-cell function.International journal of molecular sciences · 2015Review
- Grg3/TLE3 and Grg1/TLE1 induce monohormonal pancreatic β-cells while repressing α-cell functions.Diabetes · 2014Article
- Cooperation between HMGA1, PDX-1, and MafA is Essential for Glucose-Induced Insulin Transcription in Pancreatic Beta Cells.Frontiers in endocrinology · 2014Article
- A novel function of Onecut1 protein as a negative regulator of MafA gene expression.The Journal of biological chemistry · 2013Article
- Article
- Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes.Current diabetes reviews · 2013Review
- Research resource: the pdx1 cistrome of pancreatic islets.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease.Vitamins and hormones · 2012Review
- Regulation of insulin gene transcription by multiple histone acetyltransferases.DNA and cell biology · 2012Article
- ATF2 interacts with beta-cell-enriched transcription factors, MafA, Pdx1, and beta2, and activates insulin gene transcription.The Journal of biological chemistry · 2011Article
- miRNAs control insulin content in pancreatic β-cells via downregulation of transcriptional repressors.The EMBO journal · 2011Article
- Hnf1α (MODY3) regulates β-cell-enriched MafA transcription factor expression.Molecular endocrinology (Baltimore, Md.) · 2011Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin gene transcription is a unique feature of the pancreatic beta cells and is increased in response to glucose. The recent cloning of insulin promoter factor 1 (IPF1) and somatostatin transcription factor 1 (STF1) unexpectedly revealed that these are mouse and rat homologues of the same protein mediating transactivation through binding of CT box-like elements in rat insulin 1 and somatostatin promoter/enhancer regions, respectively. By using oligonucleotides representing each of the three CT boxes of the human insulin (HI) gene enhancer and nuclear extracts from the mouse islet tumor cell lines beta TC3 and alpha TC1, we have identified a beta-cell-specific binding activity as reported for IPF1, which has maximal affinity toward the CT2 box. However, in pluripotent, HI-transfected rat islet tumor cells, NHI-6F, this binding activity is present prior to induction of (human) insulin gene transcription. Its migration is identical to that of in vitro translated STF1 in electrophoretic mobility-shift assays; it is specifically recognized by anti-STF1 antibodies and has an apparent molecular mass of 46 kDa. Mutation of the CT2 box decreases transcriptional activity of a HI reporter plasmid by approximately 65% in beta TC3 cells and blocks the glucose response in isolated newborn rat islet cells. Furthermore, cotransfection with STF1 cDNA into the glucagon-producing alpha TC1 cells increases the activity of the HI enhancer 4- to 5-fold, suggesting that STF1/IPF1 can confer on alpha TC1 cells the ability to transcribe the HI gene. We conclude that STF1/IPF1 is a necessary but not sufficient key regulator of insulin gene activity, possibly also involved in glucose-regulated transcription.
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