ArticleThe Biochemical journal1999
Upstream stimulatory factor regulates Pdx-1 gene expression in differentiated pancreatic beta-cells.
Article in The Biochemical journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 58 citations in OpenAlex.
- Targeting the Epigenetic Marks in Type 2 Diabetes Mellitus: Will Epigenetic Therapy Be a Valuable Adjunct to Pharmacotherapy?Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Epigenetic modification and therapeutic targets of diabetes mellitus.Bioscience reports · 2020Review
- Sufu- and Spop-mediated downregulation of Hedgehog signaling promotes beta cell differentiation through organ-specific niche signals.Nature communications · 2019Article
- Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells.Scientific reports · 2017Article
- Role of upstream stimulatory factor 2 in diabetic nephropathy.Frontiers in biology · 2015Article
- A novel SMAD family protein, SMAD9 is involved in follicular initiation and changes egg yield of geese via synonymous mutations in exon1 and intron2.Molecular biology reports · 2015Article
- Intrauterine Growth Retardation - A Developmental Model of Type 2 Diabetes.Drug discovery today. Disease models · 2013Article
- Epigenetics and diabetes treatment: an unrealized promise?Trends in endocrinology and metabolism: TEM · 2012Review
- Exendin-4 increases histone acetylase activity and reverses epigenetic modifications that silence Pdx1 in the intrauterine growth retarded rat.Diabetologia · 2011Article
- Suppression of the pancreatic duodenal homeodomain transcription factor-1 (Pdx-1) promoter by sterol regulatory element-binding protein-1c (SREBP-1c).The Journal of biological chemistry · 2011Article
- Genome-wide association study identifies Loci for body composition and structural soundness traits in pigs.PloS one · 2011Article
- ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells.Biochemical and biophysical research communications · 2010Article
- Glycated albumin upregulates upstream stimulatory factor 2 gene transcription in mesangial cells.American journal of physiology. Renal physiology · 2010Article
- Epigenetic mechanisms in the development of type 2 diabetes.Trends in endocrinology and metabolism: TEM · 2010Review
- Developmental origins of adult disease.Pediatric clinics of North America · 2009Review
- Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1.The Journal of clinical investigation · 2008Article
- High glucose levels upregulate upstream stimulatory factor 2 gene transcription in mesangial cells.Journal of cellular biochemistry · 2008Article
- Transcriptional regulation of the distal promoter of the rat pyruvate carboxylase gene by hepatocyte nuclear factor 3beta/Foxa2 and upstream stimulatory factors in insulinoma cells.The Biochemical journal · 2007Article
- Upstream stimulatory factor (USF) and neurogenic differentiation/beta-cell E box transactivator 2 (NeuroD/BETA2) contribute to islet-specific glucose-6-phosphatase catalytic-subunit-related protein (IGRP) gene expression.The Biochemical journal · 2003Article
- Characterization of the human liver fructose-1,6-bisphosphatase gene promoter.The Biochemical journal · 2000Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The homeobox gene Pdx-1 plays a key role in the development of the pancreas. In the adult, however, expression of the Pdx-1 gene is restricted to pancreatic beta-cells and endocrine cells of duodenal epithelium. Recently, the transcription factor, upstream stimulatory factor (USF), has been shown to bind in vitro to a mutationally sensitive E-box motif within the 5'-flanking region of the Pdx-1 gene [Sharma, Leonard, Lee, Chapman, Leiter and Montminy (1996) J. Biol. Chem. 271, 2294-2299]. In the present study, we show that USF not only binds to the Pdx-1 gene promoter but also functionally regulates the expression of the Pdx-1 gene in differentiated pancreatic beta-cells. Adenovirus-mediated overexpression of a dominant negative form of USF2 decreased binding of endogenous USF to the E-box element by approximately 90%. This reduction in endogenous USF binding led to a greater than 50% decrease in Pdx-1 gene promoter activity, which, in turn, resulted in marked reductions in Pdx-1 mRNA and protein levels. Importantly, the lower Pdx-1 protein levels led to a greater than 50% reduction in Pdx-1 binding activity to the A3 element on the insulin gene promoter, and a significant reduction in insulin mRNA levels. Overall, our results show that USF functionally regulates Pdx-1 gene expression in differentiated pancreatic beta-cells and provide the first functional data for a role of USF in the regulation of a normal cellular gene.
Indexed as
Identifiers
10393088PMC1220362W2072616622What OpenQuestion holds
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.