Analysis of p53-regulated gene expression patterns using oligonucleotide arrays

Oligonucleotide microarrays were employed to quantitate mRNA levels from a large number of genes regulated by the p53 transcription factor. Responses to DNA damage and to zinc-inducible p53 were compared for their transcripti on patterns in cell culture. A cluster analysis of these data demonstrates that genes induced by gamma radiation, UV radiation, and the zinc-induced p 53 form distinct sets and subsets with a few genes in common to all these t reatments. Cell type- or cell line-specific p53 responses were detected. Wh en p53 proteins were induced with zinc, the kinetics of induction or repres sion of mRNAs from p53-responsive genes fell into eight distinct classes, f ive different kinetics of induction, and three different kinetics of repres sion. In addition, low levels of p53 in a cell induced or repressed only a subset of genes observed at higher p53 levels. The results of this study de monstrate that the nature of the p53 response in diverse mRNA species depen ds on the levels of p53 protein in a cell, the type of inducing agent or ev ent, and the cell type employed. Of 6000 genes examined for p53 regulatory responses, 107 induced and 54 repressed genes fell into categories of apopt osis and growth arrest, cytoskeletal functions, growth factors and their in hibitors, extracellular matrix, and adhesion genes.