Characterization of a novel Foxa (hepatocyte nuclear factor-3) site in the glucagon promoter that is conserved between rodents and humans

The pancreatic islet hormone glucagon stimulates hepatic glucose production and thus maintains blood glucose levels in the fasting state. Transcription factors of the Foxa [Fox (forkhead box) subclass A; also known as HNF-3 (hepatocyte nuclear factor-3)] family are required for cell-specific activation of the glucagon gene in pancreatic islet α-cells. However, their action on the glucagon gene is poorly understood. In the present study, comparative sequence analysis and molecular characterization using protein–DNA binding and transient transfection assays revealed that the well-characterized Foxa-binding site in the G2 enhancer element of the rat glucagon gene is not conserved in humans and that the human G2 sequence lacks basal enhancer activity. A novel Foxa site was identified that is conserved in rats, mice and humans. It mediates activation of the glucagon gene by Foxa proteins and confers cell-specific promoter activity in glucagon-producing pancreatic islet α-cell lines. In contrast with previously identified Foxa-binding sites in the glucagon promoter, which bind nuclear Foxa2, the novel Foxa site was found to bind preferentially Foxa1 in nuclear extracts of a glucagon-producing pancreatic islet α-cell line, offering a mechanism that explains the decrease in glucagon gene expression in Foxa1-deficient mice. This site is located just upstream of the TATA box (between −30 and −50), suggesting a role for Foxa proteins in addition to direct transcriptional activation, such as a role in opening the chromatin at the start site of transcription of the glucagon gene

Studies in Greek epigraphy and history in honor of Stefen V. Tracy

Ce recueil d'articles en épigraphie grecque est destiné à honorer l'œuvre de Stephen V. Tracy dont la recherche méticuleuse sur les "mains" - ou styles - des graveurs a transformé notre perception des inscriptions d'Attique et d'au-delà. Les vingt-neuf érudits qui ont contribué à ce volume présentent des articles qui dévoilent de nouvelles inscriptions ou de nouvelles études sur des textes connus depuis longtemps, mais aussi traitent de questions historiques, religieuses et sociales. Ainsi sont étudiées la Grèce, la Mer Egée et l'Asie Mineure occidentale sur une période qui s'étend de l'époque archaïque à l'Empire romain. Le point commun de ces Mélanges réside dans le caractère central de l'épigraphie, tant dans les problèmes soulevés que dans la conviction qu'un soin minutieux porté au moindre détail d'un témoignage épigraphique peut élargir et enrichir notre compréhension de l'histoire grecque.This collection of studies in Greek epigraphy honors the work of Stephen V. Tracy. His meticulous research on the hands of Attic letter-cutters has transformed the way we think about Greek inscriptions in Attica and beyond. The twenty-nine scholars who have contributed to this volume offer papers ranging from publication of new inscriptions and studies of others long-known to wide-ranging discussions of historical, religious, and social matters. Chronologically and geographically they cover Greece, the Aegean, and western Asia Minor from the Archaic period to the Roman Empire. What unites the work here offered to Tracy is the centrality of epigraphy to the questions addressed and conviction that careful attention to even the smallest details of the epigraphic evidence can advance our understanding of the Greek past in rich and unexpected ways