HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Christoffels, V. M. Articles by Lamers, W. H. Search for Related Content PubMed PubMed Citation Articles by Christoffels, V. M. Articles by Lamers, W. H. Social Bookmarking                      What's this?

Volume 271, Number 49, Issue of December 6, 1996 pp. 31243-31250
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

The Upstream Regulatory Region of the Carbamoyl-phosphate Synthetase I Gene Controls Its Tissue-specific, Developmental, and Hormonal Regulation in Vivo

(Received for publication, April 10, 1996, and in revised form, September 4, 1996)

Vincent M. Christoffels , Maurice J. B. van den Hoff , Marinus C. Lamers ^§ , Marian A. van Roon ^¶ , Piet A. J. de Boer , Antoon F. M. Moorman and Wouter H. Lamers

From the  University of Amsterdam, Department of Anatomy and Embryology, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands, ^§ Max-Planck-Institut für Immunbiologie, Stübenweg 51, D-79108 Freiburg, Germany, and the ^¶ Academical Medical Center, Genetically Modified Mice Facility, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

The carbamoyl-phosphate synthetase I gene is expressed in the periportal region of the liver, where it is activated by glucocorticosteroids and glucagon (via cyclic AMP), and in the crypts of the intestinal mucosa. The enhancer of the gene is located 6.3 kilobase pairs upstream of the transcription start site and has been shown to direct the hormone-dependent hepatocyte-specific expression in vitro. To analyze the function of the upstream region in vivo, three groups of transgenic mice were generated. In the first group the promoter drives expression of the reporter gene, whereas the promoter and upstream region including the far upstream enhancer drive expression of the reporter gene in the second group. In the third group the far upstream enhancer was directly coupled to a minimized promoter fragment. Reporter-gene expression was virtually undetectable in the first group. In the second group spatial, temporal, and hormonal regulation of expression of the reporter gene and the endogenous carbamoyl-phosphate synthetase gene were identical. The third group showed liver-specific periportal reporter gene expression, but failed to activate expression in the intestine. These results show that the upstream region of the carbamoyl-phosphate synthetase gene controls four characteristics of its expression: tissue specificity, spatial pattern of expression within the liver and intestine, hormone sensitivity, and developmental regulation. Within the upstream region, the far upstream enhancer at 6.3 kilobase pairs is the determinant of the characteristic hepatocyte-specific periportal expression pattern of carbamoyl-phosphate synthetase.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. K. Peyton, T. Ramesh, and B. T. Spear Position-dependent activity of alpha -fetoprotein enhancer element III in the adult liver is due to negative regulation PNAS, September 19, 2000; (2000) 200290397. [Abstract] [Full Text]

				V. M. Christoffels, T. Grange, K. H. Kaestner, T. J. Cole, G. J. Darlington, C. M. Croniger, and W. H. Lamers Glucocorticoid Receptor, C/EBP, HNF3, and Protein Kinase A Coordinately Activate the Glucocorticoid Response Unit of the Carbamoylphosphate Synthetase I Gene Mol. Cell. Biol., November 1, 1998; 18(11): 6305 - 6315. [Abstract] [Full Text]

				V. M. Christoffels, P. E. M. H. Habets, A. T. Das, D. E. W. Clout, M. A. van Roon, A. F. M. Moorman, and W. H. Lamers A Single Regulatory Module of the Carbamoylphosphate Synthetase I Gene Executes Its Hepatic Program of Expression J. Biol. Chem., December 15, 2000; 275(51): 40020 - 40027. [Abstract] [Full Text] [PDF]

				D. K. Peyton, T. Ramesh, and B. T. Spear Position-dependent activity of alpha -fetoprotein enhancer element III in the adult liver is due to negative regulation PNAS, September 26, 2000; 97(20): 10890 - 10894. [Abstract] [Full Text] [PDF]