STRUCTURAL AND FUNCTIONAL SIMILARITIES BETWEEN THE PROMOTERS FOR MOUSE TENASCIN AND CHICKEN CYTOTACTIN

Cytotactin/tenascin is an extracellular matrix glycoprotein expressed in a restricted anteroposterior pattern during vertebrate development and is reexpressed in the adult during wound healing, tumorigenesis, a nd nerve regeneration. previously, we have characterized the chicken c ytotactin promoter and have shown its regulation by homeobox gene prod ucts in vitro. We have now isolated the promoter for the mouse tenasci n gene in order to determine whether common or different DNA regulator y elements control the expression of this gene in these two species. L ike the chicken cytotactin gene, the mouse tenascin gene has a single RNA start site that lies 27 bp downstream of a TATA box, A 4028-bp reg ion of DNA upstream of the mouse tenascin gene was sequenced and exami ned for regulatory motifs in common with the upstream sequence from th e chicken cytotactin promoter, Two hundred thirty base pairs of the pr oximal promoter regions from both genes had an extended sequence simil arity and contained common regulatory motifs such as two tracts of hom opolymeric dA . dT sequence, an octamer motif, an ATTA (TAAT) motif wh ich is a common core sequence for binding of homeodomain transcription factors, and a TATA-box/cap-site region. Reporter gene constructs wit h various 5' deletions of the mouse tenascin upstream sequence were te sted in transient transfections of mouse NIH 3T3 and chicken embryo fi broblasts. The conserved proximal promoter region of tenascin was resp onsible for most of the positive regulatory activity. In addition, an upstream region (-2478 to -247) repressed proximal promoter activity i n mouse fibroblasts and also in chicken embryo fibroblasts. These data indicate that both the structure and function of the cytotactin/tenas cin proximal promoters have remained conserved over 250 million years.