SAGE TRANSCRIPT PROFILES FOR P53-DEPENDENT GROWTH-REGULATION

Serial analysis of gene expression (SAGE) allows for a quantitative, r epresentative, and comprehensive profile of gene expression, We have u tilized SAGE technology to contrast the differential gene expression p rofile in rat embryo fibroblast cells producing temperature-sensitive p53 tumor suppressor protein at permissive or nonpermissive temperatur es, Analysis of similar to 15 000 genes revealed that the expression o f 14 genes (P<0.001, greater than or equal to 0.03% abundance) was dep endent on functional p53 protein, whereas the expression of three gene s was significantly higher in cells producing non-functional p53 prote in, Those genes whose expression was increased by functional p53 inclu de RAS, U6 snRNA, cyclin G, EGR-1, and several novel genes, The expres sion of actin, tubulin, and HSP70 genes was elevated at the nonpermiss ive temperature for p53 function, Interestingly, the expression of sev eral genes was dependent on a non-temperature-sensitive mutant p53 sug gesting altered transcription profiles dependent on specific p53 mutan t proteins. These results demonstrate the utility of SAGE for rapidly and reproducibly evaluating global transcriptional responses within di fferent cell populations.