Control of the rat angiotensin I converting enzyme gene by CRE-like sequences
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 28...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Associação Brasileira de Divulgação Científica
2004-10-01
|
| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2004001000002 |
| _version_ | 1828158359053795328 |
|---|---|
| author | J. Xavier-Neto A.C. Pereira E.M. Oliveira A.A. Miyakawa M.L. Junqueira J.E. Krieger |
| author_facet | J. Xavier-Neto A.C. Pereira E.M. Oliveira A.A. Miyakawa M.L. Junqueira J.E. Krieger |
| author_sort | J. Xavier-Neto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T23:42:30Z |
| format | Article |
| id | doaj.art-b2d4b092ae49448b820486eb1906359c |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-04-11T23:42:30Z |
| publishDate | 2004-10-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-b2d4b092ae49448b820486eb1906359c2022-12-22T03:56:45ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2004-10-0137101441145310.1590/S0100-879X2004001000002Control of the rat angiotensin I converting enzyme gene by CRE-like sequencesJ. Xavier-NetoA.C. PereiraE.M. OliveiraA.A. MiyakawaM.L. JunqueiraJ.E. KriegerWe 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2004001000002Angiotensin converting enzymeEndotheliumcAMPCyclic AMP responsive element |
| spellingShingle | J. Xavier-Neto A.C. Pereira E.M. Oliveira A.A. Miyakawa M.L. Junqueira J.E. Krieger Control of the rat angiotensin I converting enzyme gene by CRE-like sequences Brazilian Journal of Medical and Biological Research Angiotensin converting enzyme Endothelium cAMP Cyclic AMP responsive element |
| title | Control of the rat angiotensin I converting enzyme gene by CRE-like sequences |
| title_full | Control of the rat angiotensin I converting enzyme gene by CRE-like sequences |
| title_fullStr | Control of the rat angiotensin I converting enzyme gene by CRE-like sequences |
| title_full_unstemmed | Control of the rat angiotensin I converting enzyme gene by CRE-like sequences |
| title_short | Control of the rat angiotensin I converting enzyme gene by CRE-like sequences |
| title_sort | control of the rat angiotensin i converting enzyme gene by cre like sequences |
| topic | Angiotensin converting enzyme Endothelium cAMP Cyclic AMP responsive element |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2004001000002 |
| work_keys_str_mv | AT jxavierneto controloftheratangiotensiniconvertingenzymegenebycrelikesequences AT acpereira controloftheratangiotensiniconvertingenzymegenebycrelikesequences AT emoliveira controloftheratangiotensiniconvertingenzymegenebycrelikesequences AT aamiyakawa controloftheratangiotensiniconvertingenzymegenebycrelikesequences AT mljunqueira controloftheratangiotensiniconvertingenzymegenebycrelikesequences AT jekrieger controloftheratangiotensiniconvertingenzymegenebycrelikesequences |