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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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
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Abstract	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.
AbstractList	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. 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.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.
Author	Schoneveld, Onard J.L.M. Hoogenkamp, Maarten Gaemers, Ingrid C. Lamers, Wouter H.
Author_xml	– sequence: 1 givenname: Onard J.L.M. surname: Schoneveld fullname: Schoneveld, Onard J.L.M. – sequence: 2 givenname: Ingrid C. surname: Gaemers fullname: Gaemers, Ingrid C. – sequence: 3 givenname: Maarten surname: Hoogenkamp fullname: Hoogenkamp, Maarten – sequence: 4 givenname: Wouter H. surname: Lamers fullname: Lamers, Wouter H. email: w.h.lamers@amc.uva.nl
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Snippet	As part of the urea cycle, carbamoylphosphate synthetase (CPS) converts toxic ammonia resulting from amino-acid catabolism into urea. Liver-specific and...
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SubjectTerms	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
Title	The role of proximal-enhancer elements in the glucocorticoid regulation of carbamoylphosphate synthetase gene transcription from the upstream response unit
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