High-Resolution 4C Reveals Rapid p53-Dependent Chromatin Reorganization of the CDKN1A Locus in Response to Stress

A regulatory program involving hundreds of genes is coordinated by p53 to prevent carcinogenesis in response to stress. Given the importance of chromatin loops in gene regulation, we investigated whether DNA interactions participate in the p53 stress response. To shed light on this issue, we measured the binding dynamics of cohesin in response to stress. We reveal that cohesin is remodeled at specific loci during the stress response and that its binding within genes negatively correlates with transcription. At p53 target genes, stress-induced eviction of cohesin from gene bodies is concomitant to spatial reorganization of loci through the disruption of functional chromatin loops. These findings demonstrate that chromatin loops can be remodeled upon stress and contribute to the p53-driven stress response. Additionally, we also propose a mechanism whereby transcription-coupled eviction of cohesin from CDKN1A might act as a molecular switch to control spatial interactions between regulatory elements.p53可协调涉及数百个基因的调控程序，以在应激应答过程中预防癌变。鉴于染色质环（chromatin loops）在基因调控中的关键作用，我们探究了DNA互作是否参与p53介导的应激应答。为阐明该科学问题，我们检测了黏连蛋白（cohesin）在应激应答中的结合动态。研究发现，在应激应答期间，黏连蛋白会在特异性位点发生重塑，且其在基因体区域内的结合水平与转录活性呈负相关。在p53靶基因中，应激诱导的黏连蛋白从基因体撤离，伴随功能性染色质环的破坏所介导的位点空间重组织。上述研究结果表明，染色质环可在应激条件下发生重塑，并参与p53驱动的应激应答。此外，我们还提出了一种潜在机制：CDKN1A基因位点上的转录偶联黏连蛋白撤离，可作为分子开关调控调控元件之间的空间互作。