In this paper, the human phosphodiesterase 7A1 (hPDE7A1) promoter region was identified and functionally characterized. Transient transfection experiments indicated that a 2.9 kb fragment of the hPDE7A1 5′-flanking region, to position −2907, has strong promoter activity in Jurkat T-cells. Deletion analysis showed that the proximal region, up to position −988, contains major cis-regulatory elements of the hPDE7A1 promoter. This minimal promoter region contains a regulatory CpG island which is essential for promoter activity. The CpG island contains three potential cAMP-response-element-binding protein (CREB)-binding sites that, as judged by in vivo dimethyl sulphate (DMS) footprinting, are occupied in Jurkat T-cells. Moreover, over-expression of CREB results in increased promoter activity, but, on the other hand, promoter activity decreases when a dominant-negative form of CREB (KCREB) is over-expressed. In vivo DMS footprinting strongly indicates that other transcription factors, such Ets-2, nuclear factor of activated T-cells 1 (NFAT-1) and nuclear factor κB (NF-κB), might also contribute to the regulation of hPDE7A1 promoter. Finally, hPDE7A1 promoter was found to be induced by treatment with PMA, but not by treatment with dibutyryl cAMP or forskolin. These results provide insights into the factors and mechanisms that regulate expression of the hPDE7A gene.
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August 2003
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Research Article|
August 01 2003
Functional characterization of the human phosphodiesterase 7A1 promoter
Mònica TORRAS-LLORT;
Mònica TORRAS-LLORT
Departament de Biologia Molecular i Cellular, Institut de Biologia Molecular de Barcelona, CSIC, Jordi Girona Salgado 18-26. 08034 Barcelona, Spain
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Fernando AZORÍN
Fernando AZORÍN
1
Departament de Biologia Molecular i Cellular, Institut de Biologia Molecular de Barcelona, CSIC, Jordi Girona Salgado 18-26. 08034 Barcelona, Spain
1To whom correspondence should be addressed (e-mail fambmc@cid.csic.es).
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Publisher: Portland Press Ltd
Received:
November 22 2002
Revision Received:
April 14 2003
Accepted:
May 09 2003
Accepted Manuscript online:
May 09 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 373 (3): 835–843.
Article history
Received:
November 22 2002
Revision Received:
April 14 2003
Accepted:
May 09 2003
Accepted Manuscript online:
May 09 2003
Citation
Mònica TORRAS-LLORT, Fernando AZORÍN; Functional characterization of the human phosphodiesterase 7A1 promoter. Biochem J 1 August 2003; 373 (3): 835–843. doi: https://doi.org/10.1042/bj20021829
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