Analysis of p53-regulated gene expression patterns using oligonucleotide arrays
- Renbin Zhao1,
- Kurt Gish3,
- Maureen Murphy2,6,
- Yuxin Yin4,6,
- Daniel Notterman1,6,
- William H. Hoffman2,
- Edward Tom3,
- David H. Mack3, and
- Arnold J. Levine5,7
- 1Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544 USA; 2Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 USA; 3Genomics Research, Eos Biotechnology, South San Francisco, California 94080 USA; 4Department of Radiation Oncology, Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032 USA; 5The Rockefeller University, New York, New York 10021 USA
Abstract
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 transcription patterns in cell culture. A cluster analysis of these data demonstrates that genes induced by γ radiation, UV radiation, and the zinc-induced p53 form distinct sets and subsets with a few genes in common to all these treatments. Cell type- or cell line-specific p53 responses were detected. When p53 proteins were induced with zinc, the kinetics of induction or repression of mRNAs from p53-responsive genes fell into eight distinct classes, five different kinetics of induction, and three different kinetics of repression. 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 demonstrate that the nature of the p53 response in diverse mRNA species depends on the levels of p53 protein in a cell, the type of inducing agent or event, and the cell type employed. Of 6000 genes examined for p53 regulatory responses, 107 induced and 54 repressed genes fell into categories of apoptosis and growth arrest, cytoskeletal functions, growth factors and their inhibitors, extracellular matrix, and adhesion genes.
