Dynamic properties of enhancer and promoter during DNA damage in hepatocellular carcinoma [ChIP-Seq]

DNA damage is a critical factor contributing to tumorigenesis, however, the dynamic changes in multi-omics signatures of enhancers and promoters during the DNA damage response (DDR) remain poorly understood. In this study, we discovered that the expression levels, chromatin accessibility, and element activity of distal/proximal enhancers and promoters exhibited obvious dynamic similarity and duality of characteristics at different stages of DNA damage in hepatocellular carcinoma (HCC). Furthermore, we found that the pre-damage accessibility and activity status of enhancers and promoters played an important role in determining their regulatory features following DNA damage in HCC. Finally, we identified transcription factors (TFs) with significantly altered activity in response to DNA damage, with notable differences between p53 activity in enhancers and promoters during the DDR. Overall, these findings reveal the complex dynamic changes within cis-regulatory elements in response to DNA damage. Overall design: HepG2 cells were cultured in DMEM (Gibco, USA) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin–streptomycin. When the cell spreading rate reached 80%, the cells were cultured with complete medium containing DOX at a final concentration of 0.5µg/mL. Subsequently, the cells were treated for various durations (0h, 4h, 8h, 12h, 16h, 24h, 36h, and 48h) before samples were extracted for additional experimental validation.