72 / 2024-10-18 19:54:48

Genome-wide p53-associated chromatin interaction and transcription regulation in colon cancer

p53,in situ ChIA-PET,chromatin interactions,regulome,colon cancer

Abstract：The tumor suppressor p53, serving as a transcription factor, is pivotal in orchestrating DNA repair and cell division by regulating gene expression associated with cell-cycle arrest, DNA repair, and apoptosis. Nevertheless, the specifics of the p53 regulatory element in relation to its target gene expression remain elusive. In this study, we utilized in situ ChIA-PET method to discern p53-associated chromatin interactions in HCT116 colon cancer cells. These cells were activated by p53 status following treatment with the frequently used anti-cancer drug 5-FU. By integrating data from the RNAPII-mediated chromatin regulome and transcriptome, we distinguished two primary categories of p53-associated chromatin interaction profiles: promoter- dominant and enhancer-dominant. The promoter-dominant profile tends to be more rapidly and potently activated compared to the enhancer-dominant profile, which is typically induced later and more subtly. We further found that p53 does not alter the topologically associated domain (TAD) and A/B compartments. Moreover, we infected p53-knockout HCT116 cells with recombinant human p53 adenovirus (Ad-p53) to reinstate p53 expression and verify these two interaction profiles. In conclusion, we uncover the landscape of p53-associated chromatin interactions using 3D genome technology and propose regulatory networks for p53 involving promoter-dominant and enhancer-dominant types.