B52

TP53 (tumor protein p53; p53) regulates its target genes under various cellular stresses. By combining chromatin immunoprecipitation with oligonucleotide microarrays, we have mapped binding sites of p53 (p53-BS) under 5-FU treatment in the genome of HCT116 human colon carcinoma cells, along with those of acetylated H3 and acetylated H4. Chromatin-immunoprecipitated DNA was amplified using IVT method, and hybridized onto the Affymetrix WG10G arrays, covering non-repetitive whole human genome sequence.
 A total of 2,600, 8,000 and 12,000 high confidence (p_value < 10-5) enriched sites were observed for p53-binding, acetylated H3 and H4, respectively. There was a quite enrichment of p53 consensus motif in the p53-binding sites. Approximately, 80% of p53 binding sites were more than 10kb far from transcription start sites. However, a half of the p53-binding sites were overlapped with histone acetylation sites. Acetylated H3 were preferentially located at the 5' ends of genes, whereas acetylated H4 were distributed widely across the genome. These results provide novel insights into how p53 binding coordinates with histone modification in human.

First AACR Centennial Conference on Translational Cancer Medicine-- Nov 4-8, 2007; Singapore