Abstract
Mitochondrial aspartate aminotransferase (mAAT) is one of two key enzymes in the pathway of citrate production in prostate. Expression of mAAT is modulated by testosterone and prolactin in prostate. We cloned the promoter and 5'-flanking region of the rat mAAT gene and sequenced 2.0 kilobases of the DNA. This fragment contains the 5'-regulatory promoter region that lacks a TATA and a CCAAT box but is G+C rich. The 5'-upstream flanking region contains sequences that have high homology with the consensus glucocorticoid response element/androgen response element (ARE) and a reported ARE sequence that is different from the consensus sequence. Functional transcription studies showed that a 481-base region containing the two ARE sequences was sufficient for androgen-regulated gene expression. There are multiple transcription start sites that are regulated by testosterone in prostate. In liver, on the other hand, castration did not affect transcription from any of the start sites. Therefore, these data provide evidence that transcriptional regulation of the rat pmAAT gene occurs through an ARE located in the 5'-region. In addition, not only is gene expression modulated by testosterone, but the effect of testosterone on transcription is cell specific.
Highlights
We showed that the effects of testosterone [3, 4] and prolactin [5] on Mitochondrial aspartate aminotransferase (mAAT) were at the level of gene expression. mAAT is expressed in all tissues, it is regulated by testosterone in prostate epithelium but not in other tissues [1]
The results provide evidence that transcriptional regulation of the rat precursor mAAT (pmAAT) gene occurs through an androgen response element (ARE) located in the 5'-region
The 5' -flanking region of the pmAAT gene was isolated by screening a rat genomic library with a 500-bp fragment of the rat pmAAT eDNA (Fig. 1)
Summary
Vol 270, No 21, Issue of May 26, pp. 12629-12634, 1995 Printed in U.S.A. Androgen Modulation of Multiple Transcription Start Sites of the Mitochondrial Aspartate Aminotransferase Gene in Rat Prostate*. Franklin§ From the Department of Physiology, Dental School, University of Maryland at Baltimore, Baltimore, Maryland 21201. On the other hand, castration did not affect transcription from any of the start sites These data provide evidence that transcriptional regulation of the rat pmAAT gene occurs through an ARE located in the 5' -region. The costs of publication of this article were defrayed in part by the payment of page charges. The gene contains multiple transcription start sites that are regulated by testosterone in prostate but not in liver. We speculate that the initiation of transcription from multiple start sites contributes to the mechanism of testosterone modulation of expression of mAAT and to the tissue-specific regulation of this housekeeping gene. The results provide evidence that transcriptional regulation of the rat pmAAT gene occurs through an ARE located in the 5'-region
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