Functional analysis of the promoters of the human CaMIII calmodulin gene and of the intronless gene coding for a calmodulin-like protein.

More than 1 kb of the 5'-flanking DNA of the human CaMIII calmodulin gene and of the calmodulin-like protein (CLP) gene have been sequenced. Notable features are the absence of a TATA-box and the presence of AGGGA elements in both upstream regions, the presence of several sequences with homology to known regulatory elements (cAMP-, retinoic acid- and interferon-responsive elements) in the CLP gene, and a high G + C-content and several putative Sp1-factor-binding sites in the CaMIII gene. 1 kb of the CaMIII upstream region was driving high-level growth hormone (hGH) reporter gene expression in human teratoma and monkey COS cells. Promoter activity dropped to about 30% and 10% when only 252 bp and 114 bp, respectively, of the CaMIII sequence were present. In contrast to the CaMIII promoter, the CLP gene upstream region was driving hGH expression only in human teratoma, but not in monkey COS cells. Addition of retinoic acid to the transfected cells had minimal effects on both promoters, leading to a 10-30% decrease of activity. The results show that the human CaMIII gene contains a strong and ubiquitously active promoter, whereas the promoter of the intronless CLP gene appears to be regulated in a cell-specific manner.