Chromatin accessibility regulates chemotherapy-induced dormancy and reactivation

Cisplatin-based chemotherapy remains the standard care for chemotherapy-induced dormancy affects the overall survival of patients. The evolution of cancer cells under chemotherapy stress is regulated by transcription factors (TFs) with binding sites initially buried deep within inaccessible chromatin. The transcription machinery and dynamic epigenetic alterations during the process of dormancy-reactivation of lung cancer cells after chemotherapy need to be investigated. Here, we investigated the chromatin accessibility of lung cancer cells after cisplatin treatment, using an assay for transposase-accessible chromatin sequencing (ATAC-seq). We observed that global chromatin accessibility was extensively improved. Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST) v.2 was used to elucidate TF-target interaction during the process of dormancy and reactivation. Enhancer regions and motifs specific to key TFs STAT3, NFKB1, and KLF4 were enriched in differential loci ATAC-seq peaks of dormant and reactivated cancer cells induced by chemotherapy. The findings suggest that these key TFs regulated gene expressions during the process of dormancy and reactivation of cancer cells through altering promoter accessibility of target genes. Our study helps advance understanding of how cancer cells adapt to the accessibility.

Automated summary

This study investigated the chromatin accessibility of lung cancer cells after cisplatin treatment and used TRRUST v.2 to uncover the transcription factor-target gene interactions. The results showed that key transcription factors like STAT3, NFKB1, and KLF4 regulate gene expression during the process of dormancy and reactivation by altering the promoter accessibility of target genes.