Loop domain organization of the p53 locus in normal and breast cancer cells correlates with the transcriptional status of the TP53 and the neighboring genes.

ABSTRACT

P53 is a tumor suppressor protein critical for genome integrity. Although its control at the protein level is well known, the transcriptional regulation of the TP53 gene is still unclear. We have analyzed the organization of the TP53 gene domain using DNA arrays in several breast cancer and control cell lines. We have found that in the control breast epithelial cell line, HB2, the TP53 gene is positioned within a relatively small DNA domain, encompassing 50 kb, delimited by two nuclear matrix attachment sites. Interestingly, this domain structure was found to be radically different in the studied breast cancer cell lines, MCF7, T47D, MDA-MB-231, and BT474, in which the domain size was increased and TP53 transcription was decreased. We propose a model in which the organization of the TP53 gene domain correlates with the transcriptional status of TP53 and neighboring genes.