Allelic Variation of Reporter Gene Activation by the HRAS1 Minisatellite

Abstract

We have recently shown that constitutively expressed members of the rel /NF-κB family of transcription factors bind the HRAS1 minisatellite, VTRHRAS1. We now report that, like other NF-κB binding sites, VTRHRAS1 displays pleiotropic transcriptional regulatory activity that is promoter- and cell-type-specific. Both enhancement and suppression are restricted to the human bladder carcinoma cell line EJ, in which we have previously defined a unique form of NF-κB p50. We also observe allelic variation in functional activity: the rare a2.1 allele, one member of a class of HRAS1 alleles overrepresented in the genomes of cancer patients, possesses twofold greater enhancer activity than the low-risk alleles, a0.1, a1, and a2. Finally, VTRHRAS1 enhancer activity is upregulated by the adenovirus E1A 13S gene product, demonstrating the potential of the minisatellite for influencing gene expression through several distinct interactions with the transcriptional apparatus.