Temporal regulation of PARP1 acetylation in tumorigenesis

We examined the impact of PARP1-ATF4 interaction on cellular transcription program. ATF4 plays a pivotal role in stress response by regulating expression of diverse genes. Under genotoxic stress, the acetylation status of PARP1 at lysine 521 influences the expression of diverse genes. Also, co-depletion of ATF4 leads to the downregulation of many genes. These genes are involved in pathways related to cancer risk, such as epithelial-to-mesenchymal transition (EMT), metastasis, cell cycle regulation, and metabolic processes. To investigate the effect of PARP1 K521 deacetylation on the expression of key ATF4-regulated genes, HT29 control, PARP1 knockdown cells expressing PARP1-K521R as well as PARP1 and ATF4 double knockdown cells expressing PARP1-K521R were treated with 5 fluorouracil. We then performed gene expression analysis from data obtained from RNA-seq of these cell lines.