Transcriptional control of the human Harvey ras proto-oncogene: role of multiple elements in the promoter region.

In the promoter region of the human c-Ha-ras1 gene, multiple elements for transcriptional control are dispersed. To examine the role of each element, we made a series of deletion mutants of this promoter region, including internal deletion mutants, and measured the promoter activities of these mutants. Any two of the four Sp1-binding sites upstream from the CCAAT-box element were sufficient for the maximal activity of the c-Ha-ras1 promoter. Either one of the two Sp1-binding sites downstream from the CACCC-box element was also necessary for the maximal promoter activity. Deletion of the CCAAT-box or CACCC-box elements reduced the level of transcription to 25% or 41% of that with the wild-type promoter. These results indicated that at least three Sp1-binding sites, and the CCAAT-box and CACCC-box elements contributed in concert to the activity of the human c-Ha-ras1 promoter.