Todorov, Vladimir T. and Desch, Michael and Schubert, Thomas and Kurtz, Armin (2008) The Pal3 promoter sequence is critical for the regulation of human renin gene transcription by peroxisome proliferator-activated receptor-gamma. ENDOCRINOLOGY, 149 (9). pp. 4647-4657. ISSN 0013-7227,
Full text not available from this repository. (Request a copy)Abstract
We recently reported that human renin gene transcription is stimulated by the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-gamma in the renin-producing cell line Calu-6. The effect of PPAR gamma was mapped to two sequences in the renin promoter: a direct repeat hormone response element (HRE), which is related to the classical PPAR response element (PPRE) and a nonconsensus palindromic element with a 3-bp spacer (Pal3). We now find that PPAR gamma binds to the renin HRE. Neither the human renin HRE nor the consensus PPRE was sufficient to attain the maximal stimulation of renin promoter activity by the PPAR gamma agonist rosiglitazone. In contrast, the human renin Pal3 element mediates both the full PPAR gamma-dependent activation of transcription and the PPAR gamma-driven basal renin gene transcription. The human renin Pal3 sequence was found to selectively bind PPAR gamma and the retinoid X receptor-alpha from Calu-6 nuclear extracts. This is in contrast to the consensus PPRE, which can bind other nuclear proteins. PPAR alpha knockdown paradoxically did not attenuate the stimulation of the endogenous renin gene expression by rosiglitazone. Similarly, a deficiency of PPAR gamma did not attenuate the activation of the minimal human renin promoter, which contains the endogenous Pal3 motif. However, when the human renin Pal3 site was replaced by the consensus PPRE sequence, PPAR gamma knockdown abrogated the effect of rosiglitazone on renin promoter activity. Thus, the human renin Pal3 site appears to be critical for the PPAR gamma-dependent regulation of gene expression by mediating maximal transcription activation, particularly at the low cellular level of PPAR gamma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NECROSIS-FACTOR-ALPHA; CAMP-RESPONSIVE ELEMENT; PPAR-GAMMA; INSULIN-RESISTANCE; MESSENGER-RNA; 1,25-DIHYDROXYVITAMIN D-3; 3'-UNTRANSLATED REGION; JUXTAGLOMERULAR CELLS; VASCULAR DYSFUNCTION; CALU-6 CELLS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 07:34 |
| Last Modified: | 26 Oct 2020 07:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30333 |
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