| First Author | Schutz G | Year | 1988 |
| Journal | Mouse News Lett | Volume | 82 |
| Pages | 156 | Mgi Jnum | J:14231 |
| Mgi Id | MGI:62403 | Citation | Schutz G, et al. (1988) Hormone-dependent and cell-specific expression of the tyrosine aminotransferase gene. Mouse News Lett 82:156 |
| abstractText | Full text of MNL contribution: Hormone-Dependent and Cell-Specific Expression of the Tyrosine Aminotransferase Gene. G. Schutz, U. Strahle, A. Munsterberg, W. Schmid, G. Kelsey, F. Stewart and M. Boshart. Institute of Cell and Tumor Biology, German Cancer Research Center, Im Neuenheimer Feld 280,6900 Heidelberg, West Germany. Expression of the tyrosine aminotransferase (TAT) gene is restricted to the parenchymal cells of liver and is characterized by induction in the immediate postnatal period. Transcriptional activation is induced by glucocorticoids and glucagon (via cAMP) and is under control of two distinct transacting loci. Two glucocorticoid response elements (GRE), which affect transcription of the gene cooperatively, have been identified by gene-transfer and receptor footprinting experiments. A 15 bp partial palindromic sequence within the footprint is sufficient to elicit a glucocorticoid response when linked to a heterologous promoter. Analyses of the sequence requirements for induction by glucocorticoids, progesterone, testosterone, estradiol and ecdysterone led to the conclusion that the sequences recognized by the respective receptors are either identical or closely related. A single GRE can activate transcription without other promoter upstream elements when in proximity to the TATA-box. When positioned further upstream (-351), a single receptor binding site is not sufficient, but requires interaction with a second receptor molecule or other transcription factors (CCAAT-box and CCCAC-box binding proteins). In order to address the question whether a particular segment of the receptor protein might be involved in cooperativity of the glucocorticoid receptor with itself or with a CCAAT-box transcription factor, we cotransfected reporter plasmids containing either two GREs or one GRE and the CCAAT-box sequence with plasmids encoding either the entire receptor protein or a receptor from which the NH2-terminal part had been deleted. The altered receptor is still capable to mediate the cooperative effect exerted by two GREs, but not of the combination of one GRE with a CCAAT-box. These data strongly suggest that the NH2-terminal part of the glucocorticoid receptor is required for interaction with other transcription factors. In order to identify sequences important for cell-specific expression, TAT gene recombinants are transferred into hepatoma cells and mice. Expression in hepatoma cells is strongly stimulated by sequences located far upstream from the start site of transcription. The sequences important for cell-specific expression do also mediate induction by cAMP and the effect of the tissue-specific extinguisher, tse-1, which is responsible for the extinction of TAT gene expression in intertypic hybrids. |
