Abstract
Background Transcription factors orchestrate the cellular response to stimuli by binding specifically to DNA and activating associated genes. In the DNA damage response, the tumor suppressor p53 regulates much of the transcriptional response and has been suggested to selectively regulate gene expression in different contexts. However, comparison between genome-wide studies shows a large overlap between p53 bound loci and thus questions this selectivity.
Results To systematically assess the cell type specificity of p53, we directly measured its association with DNA in 12 p53 wild-type cell lines in response to ionizing radiation. We found that the vast majority of bound sites are occupied across all cells lines uniformly. Gene expression, on the other hand showed substantial variability between cell lines. The coherence of our dataset, allowed us to identify a small subset of binding sites that appeared in just one or a few cell lines. We found that intrinsic chromatin accessibility of a cell line explained these differential p53 binding preferences. Moreover, we were able to manipulate p53 binding by altering chromatin state.
Conclusion Our results show the limited contribution of genomic sequence to p53 binding and suggest that in vivo factors including chromatin accessibility largely regulate its binding.