Identification of Direct p73 Target Genes Combining DNA Microarray and Chromatin Immunoprecipitation Analyses

• Published in: The Journal of biological chemistry Vol. 277; no. 45; pp. 43359 - 43368
• Main Authors: Fontemaggi, Giulia, Kela, Itai, Amariglio, Ninette, Rechavi, Gideon, Krishnamurthy, Janakiraman, Strano, Sabrina, Sacchi, Ada, Givol, David, Blandino, Giovanni
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 08.11.2002
• Subjects: Base Sequence; Carcinoma, Non-Small-Cell Lung; Chromatin - ultrastructure; DNA Primers; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Genes, p53; Genes, Tumor Suppressor; Humans; Lung Neoplasms; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oligonucleotide Array Sequence Analysis; Phenotype; Polymerase Chain Reaction; Promoter Regions, Genetic; Recombinant Proteins - metabolism; Restriction Mapping; Transfection; Tumor Cells, Cultured; Tumor Protein p73; Tumor Suppressor Proteins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M205573200

The newly discovered p53 family member, p73, has a striking homology to p53 in both sequence and modular structure. Ectopic expression of p73 promotes transcription of p53 target genes and recapitulates the most characterized p53 biological effects such as growth arrest, apoptosis, and differentiation. Unlike p53-deficient mice that develop normally but are subject to spontaneous tumor formation, p73-deficient mice exhibit severe defects in the development of central nervous system and suffer from inflammation but are not prone to tumor development. These phenotypes suggest different biological activities mediated by p53 and p73 that might reflect activation of specific sets of target genes. Here, we have analyzed the gene expression profile of H1299 cells after p73α or p53 activation using oligonucleotide microarrays capable of detecting ∼11,000 mRNA species. Our results indicate that p73α and p53 activate both common and distinct groups of genes. We found 141 and 320 genes whose expression is modulated by p73α and p53, respectively. p73α up-regulates 85 genes, whereas p53 induces 153 genes, of which 27 are in common with p73α. Functional classification of these genes reveals that they are involved in many aspects of cell function ranging from cell cycle and apoptosis to DNA repair. Furthermore, we report that some of the up-regulated genes are directly activated by p73α or p53.