A high-resolution analysis of chromatin structure along p53 sequences

A detailed investigation of how nucleosomes are formed and arranged on the DNA sequence is a prerequisite to understanding the molecular mechanisms of DNA-dependent processes such as transcription, replication, DNA repair, and mutagenesis. In this report we analyzed the chromatin structure of exons 5-8 of the p53 gene in human fibroblasts. We mapped at the nucleotide level the positions of DNase I and micrococcal nuclease cleavage sites in permeabilized cells. Areas of clear DNase I protection, which would be indicative of the binding of sequence-specific proteins, were not detected. Instead, the micrococcal nuclease and DNase digestion patterns suggested that this region was covered by nucleosomes and that two areas spanning exons 5 and 6 are occupied preferentially. These nucleosomes could influence DNA damage distribution, repair of certain lesions, and other aspects of the mutagenesis process in p53 sequences.