| First Author | Ishiguro H | Year | 1998 |
| Journal | J Biol Chem | Volume | 273 |
| Issue | 34 | Pages | 21941-9 |
| PubMed ID | 9705334 | Mgi Jnum | J:49248 |
| Mgi Id | MGI:1277037 | Doi | 10.1074/jbc.273.34.21941 |
| Citation | Ishiguro H, et al. (1998) Identification and characterization of a novel phorbol ester-responsive DNA sequence in the 5'-flanking region of the human dopamine beta-hydroxylase gene. J Biol Chem 273(34):21941-9 |
| abstractText | The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), enhances transcription of many eukaryotic genes, including that for dopamine beta-hydroxylase (DBH). In the present study, we report identification and characterization of a novel sequence motif residing in the 5'-flanking region of the human DBH gene, which mediates transcriptional induction by TPA. Deletional analyses indicated the promoter region between -223 and -187 base pairs to be critical. Whereas this region does not contain any putative regulatory motifs with significant sequence homology to the AP-1 motif, extensive deletional and site-directed mutational analyses indicated that a sequence between -210 and -199 base pairs, 5'-ATCCGCCTGTCT-3', may represent a novel TPA-response element (TRE). In addition, alteration of the YY1-binding site decreased TPA-mediated induction of the DBH promoter activity, suggesting that contiguous cis-regulatory element(s) cooperate with this novel sequence motif. Furthermore, insertional mutation analyses between the YY1-binding site and the cyclic AMP-responsive element indicated that the stereospecificity of these motifs is important for intact transcriptional induction by TPA. Taken together, these data suggest that transcriptional up-regulation of the human DBH gene in response to TPA requires coordination of a novel TRE (human DBH TRE, hDTRE), cyclic AMP-responsive element, and the YY1-binding site. |
