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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Control of the rat angiotensin I converting enzyme gene by CRE-like sequences

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Author(s):
J. Xavier-Neto [1] ; A.C. Pereira [2] ; E.M. Oliveira [3] ; A.A. Miyakawa [4] ; M.L. Junqueira [5] ; J.E. Krieger [6]
Total Authors: 6
Affiliation:
[1] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil
[2] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil
[3] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil
[4] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil
[5] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil
[6] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil
Total Affiliations: 6
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 37, n. 10, p. 1441-1453, 2004-10-00.
Abstract

We characterized the role of potential cAMP-responsive elements (CRE) in basal and in induced angiotensin converting enzyme (ACE) gene promoter activity in order to shed light on the regulation of somatic ACE expression. We identified stimulators and repressors of basal expression between 122 and 288 bp and between 415 and 1303 bp upstream from the transcription start site, respectively, using a rabbit endothelial cell (REC) line. These regions also contained elements associated with the response to 8BrcAMP. When screening for CRE motifs we found pCRE, a proximal sequence between 209 and 222 bp. dCRE, a distal tandem of two CRE-like sequences conserved between rats, mice and humans, was detected between 834 and 846 bp. Gel retardation analysis of nuclear extracts of REC indicated that pCRE and dCRE bind to the same protein complexes as bound by a canonical CRE. Mutation of pCRE and dCRE in REC established the former as a positive element and the latter as a negative element. In 293 cells, a renal cell line, pCRE and dCRE are negative regulators. Co-transfection of ATF-2 or ATF-2 plus c-Jun repressed ACE promoter activity, suggesting that the ACE gene is controlled by cellular stress. Although mapping of cAMP responsiveness was consistent with roles for pCRE and dCRE, mutation analysis indicated that they were not required for cAMP responsiveness. We conclude that the basal activity of the somatic ACE promoter is controlled by proximal and distal CREs that can act as enhancers or repressors depending on the cell context. (AU)

FAPESP's process: 01/00009-0 - An integrated approach for the dissection of primary hypertension: molecular and functional characterization of the cardiovascular system
Grantee:Eduardo Moacyr Krieger
Support Opportunities: Research Projects - Thematic Grants