A purine-rich sequence in the human BM-40 gene promoter region is a prerequisite for maximum transcription

BM-40 (osteonectin, SPARC [secreted protein, acidic, rich in cysteine]) is a highly conserved, matrix-associated protein that is found in basement membranes, bones and remodeling tissues throughout vertebrate evolution. We are reporting the characterization of the 5' end of the human BM-40 gene. Sequence comparison of the 5' region revealed significant homologies with the bovine and murine genes, including a purine-rich stretch composed of two boxes, GGA-box 1 and 2, separated by a pyrimidine-rich spacer element. Transfection analyses of the human BM-40 promoter provide strong evidence that this region comprises several distinct regulatory domains, to which different functions can be assigned. GGA-box 1 is thereby absolutely required and sufficient by itself for maximal BM-40 transcriptional activity, whereas the spacer element has a down-regulatory effect. Comparative transfection analyses in human cell lines, positive or negative for BM-40 transcripts, indicate that the GGA-box sequences in the human promoter, in contrast to the bovine promoter, do not significantly contribute to cell-type specific expression in human cells.