Investigation upon the state of p53 as well as interaction partners, in so much as can be learned from using the multi-component v5-dTag system.

Chromatin modifications provide additional context-dependence for DNA sequence-based gene regulation. Binding sites of the transcription factor (TF) and important tumour suppressor p53 are unusually diverse with regards to their chromatin accessibility and histone modifications, suggesting different modes of binding. Here, we show that the ability of p53 to open chromatin and activate its target genes is locally restricted by its cofactor Trim24. The histone-binding domains of Trim24 limits the role of p53 at closed chromatin but not at accessible chromatin where Trim24 is blocked by histone 3 methylation at lysine 4. In turn, p53 regulates gene expression as a function of the naïve chromatin state prior to activation. These findings establish a novel mode of gene regulation by p53 in closed chromatin and illustrate how histone modification sensing cofactors can bridge local chromatin state and TF potency.