NDLI: A transcription factor regulatory circuit in differentiated pancreatic cells.

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A transcription factor regulatory circuit in differentiated pancreatic cells.

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A transcription factor regulatory circuit in differentiated pancreatic cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Boj, S. F. Maestro, M. A. Ferrer, J. Parrizas, M.
Description	Author Affiliation: Boj SF ( Endocrinology and Hormonal Biochemistry Units, Hospital Clinic Universitari, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Villarroel 170, 08036 Barcelona, Spain.);
Abstract	Mutations in the human genes encoding hepatocyte nuclear factors (HNF) 1alpha, 1beta, 4alpha, and IPF1(PDX1/IDX1/STF1) result in pancreatic beta cell dysfunction and diabetes mellitus. In hepatocytes, hnf4alpha controls the transcription of hnf1alpha, suggesting that this same interaction may operate in beta cells and thus account for the common diabetic phenotype. We show that, in pancreatic islet and exocrine cells, hnf4alpha expression unexpectedly depends on hnf1alpha. This effect is tissue-specific and mediated through direct occupation by hnf1alpha of an alternate promoter located 45.6 kb from the previously characterized hnf4alpha promoter. Hnf1alpha also exerts direct control of pancreatic-specific expression of hnf4gamma and hnf3gamma. Hnf1alpha dependence of hnf4alpha, hnf4gamma, hnf3gamma, and two previously characterized distal targets (glut2 and pklr) is established only after differentiated cells arise during pancreatic embryonic development. These studies define an unexpected hierarchical regulatory relationship between two genes involved in human monogenic diabetes in the cells, which are relevant to its pathophysiology. Furthermore, they indicate that hnf1alpha is an essential component of a transcription factor circuit whose role may be to maintain differentiated functions of pancreatic cells.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	25
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA-Binding Proteins Homeodomain Proteins Nuclear Proteins Pancreas Cytology Metabolism Transcription Factors Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cell Differentiation DNA Genetics Diabetes Mellitus, Type 2 Embryology Gene Expression Regulation Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 1-beta Hepatocyte Nuclear Factor 4 Islets Of Langerhans Mice Mice, Knockout Molecular Sequence Data Mutation Phosphoproteins Promoter Regions, Genetic RNA, Messenger Tissue Distribution Trans-Activators Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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