The role of proximal-enhancer elements in the glucocorticoid regulation of carbamoylphosphate synthetase gene transcription from the upstream response unit

As part of the urea cycle, carbamoylphosphate synthetase (CPS) converts toxic ammonia resulting from amino-acid catabolism into urea. Liver-specific and glucocorticoid-dependent expression of the gene involves a distal enhancer, a promoter-proximal enhancer, and the minimal promoter itself. When cha...

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Bibliographic Details
Published in:Biochimie Vol. 87; no. 11; pp. 1033 - 1040
Main Authors: Schoneveld, Onard J.L.M., Gaemers, Ingrid C., Hoogenkamp, Maarten, Lamers, Wouter H.
Format: Journal Article
Language:English
Published: France Elsevier Masson SAS 01.11.2005
Subjects:
Animals
Base Sequence
Carbamoyl-Phosphate Synthase (Ammonia) - biosynthesis
Carbamoylphosphate synthetase
CCAAT-Enhancer-Binding Proteins - genetics
Cercopithecus aethiops
COS Cells
Distal enhancer
Electrophoretic Mobility Shift Assay
Enhancer Elements, Genetic - physiology
GAGA-box
Gene Expression Regulation, Enzymologic - genetics
Glucocorticoid-responsive element
Glucocorticoid-responsive unit
Glucocorticoids - pharmacology
Liver Neoplasms, Experimental
Models, Genetic
Molecular Sequence Data
Proximal enhancer
Rats
Receptors, Glucocorticoid - metabolism
Transcription, Genetic - physiology
Transcriptional Activation
Transfection
Tumor Cells, Cultured
GAGA-box
Carbamoylphosphate synthetase
Distal enhancer
Glucocorticoid-responsive element
Glucocorticoid-responsive unit
Proximal enhancer
ISSN:0300-9084, 1638-6183
Online Access:Get full text
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Summary:As part of the urea cycle, carbamoylphosphate synthetase (CPS) converts toxic ammonia resulting from amino-acid catabolism into urea. Liver-specific and glucocorticoid-dependent expression of the gene involves a distal enhancer, a promoter-proximal enhancer, and the minimal promoter itself. When challenged with glucocorticoids, the glucocorticoid-responsive unit (GRU) in the distal enhancer of the carbamoylphosphate-synthetase gene can only activate gene expression if, in addition to the minimal promoter, the proximal enhancer is present. Here, we identify and characterise two elements in the proximal CPS enhancer that are involved in glucocorticoid-dependent gene activation mediated by the GRU. A purine-rich stretch forming a so-called GAGA-box and a glucocorticoid-response element (GRE) are both crucial for the efficacy of the GRU and appear to constitute a promoter-proximal response unit that activates the promoter. The glucocorticoid response of the CPS gene is, therefore, dependent on the combined action of a distal and a promoter-proximal response unit.
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ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2005.02.015