Glucose-dependent Liver Gene Expression in Upstream Stimulatory Factor 2 −/− Mice

Upstream stimulatory factors (USF) 1 and 2 belong to the Myc family of transcription factors characterized by a basic/helix loop helix/leucine zipper domain responsible for dimerization and DNA binding. These ubiquitous factors form homo- and heterodimers and recognize in vitro a CACGTG core sequenc...

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Published in:The Journal of biological chemistry 1997-08, Vol.272 (35), p.21944-21949
Main Authors: Vallet, Virginie S., Henrion, Alexandra A., Bucchini, Danielle, Casado, Marta, Raymondjean, Michel, Kahn, Axel, Vaulont, Sophie
Format: Article
Language:English
Subjects:
Animals
Dietary Carbohydrates - pharmacology
Dimerization
DNA-Binding Proteins - physiology
Gene Expression
Gene Targeting
Glucose - metabolism
Helix-Loop-Helix Motifs
Liver - embryology
Liver - metabolism
Mice
Mice, Knockout
Nuclear Proteins
Promoter Regions, Genetic
Proteins - genetics
Pyruvate Kinase - genetics
RNA, Messenger - metabolism
Transcription Factors - physiology
Upstream Stimulatory Factors
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Summary:Upstream stimulatory factors (USF) 1 and 2 belong to the Myc family of transcription factors characterized by a basic/helix loop helix/leucine zipper domain responsible for dimerization and DNA binding. These ubiquitous factors form homo- and heterodimers and recognize in vitro a CACGTG core sequence termed E box. Through binding to E boxes of target genes, USF factors have been demonstrated to activate gene transcription and to enhance expression of some genes in response to various stimuli. In particular, in the liver USF1 and USF2 have been shown to bind in vitroglucose/carbohydrate response elements of glycolytic and lipogenic genes and have been proposed, from ex vivo experiments, to be involved in their transcriptional activation by glucose. However, the direct involvement of these factors in gene expression and nutrient gene regulation in vivo has not yet been demonstrated. Therefore, to gain insight into the specific role of USF1 and USF2in vivo, and in particular to determine whether the USF products are required for the response of genes to glucose, we have created, by homologous recombination, USF2 −/− mice. In this paper, we provide the first evidence that USF2 proteins are required in vivo for a normal transcriptional response of L-type pyruvate kinase and Spot 14 genes to glucose in the liver.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.35.21944