ChIP-on-chip analysis of in vivo mutant p53 binding to selected gene promoters

Stefania Dell'Orso, Giulia Fontemaggi, Perry Stambolsky, Frauke Goeman, Christine Voellenkle, Massimo Levrero, Sabrina Strano, Varda Rotter, Moshe Oren, Giovanni Blandino

Research output: Contribution to journalArticle

Abstract

Growing evidence shows that mutant p53 proteins, which are present in many human tumors, gain oncogenic activities that can actively contribute to tumorigenesis. Mutant p53 proteins have been extensively shown to affect the expression of several genes involved in various aspects of cancer biology. We show here the ChIP-on-chip analysis of mutant p53 binding to a set of 154 promoters, composed of both validated and putative mutant p53 target genes. By using the chromatin obtained from mutant p53R175H-immunoprecipitation in proliferating SKBr3 breast cancer cells, we found that mutant p53 binds to 40 of the 154 promoters analyzed. siRNA-mediated mutant p53 knock-down modulates the transcript abundance of some of these target genes. Two-thirds of the mutant p53-bound promoters were also engaged by either p300 or PCAF acetyl-transferases, strongly indicating the presence of transcriptionally active complexes. We also found that NF-kB binding sites are overrepresented among the mutant p53-bound promoters; a ChIP-on-chip analysis confirmed that NF-kB p65 binds to 27 of the mutant p53-bound promoters, indicating that mutant p53 could influence the transcriptional output of these NF-kB target genes.

Original languageEnglish
Pages (from-to)305-312
Number of pages8
JournalOMICS A Journal of Integrative Biology
Volume15
Issue number5
DOIs
Publication statusPublished - May 1 2011

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Genetics
  • Molecular Biology
  • Molecular Medicine

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