Epigenomic changes under cellular stress

The cell stress response is a multifaceted and evolutionarily conserved pathway aimed at inducing an anti-stress proteome. In eukaryotic organisms, the cascade of signals involved in this response has been significantly studied at the transcriptional, translational, and post-translational levels, including at the level of alternative polyadenylation (APA). APA can be regulated by DNA-methylation-sensitive chromatin looping. Herein, we examine the role of DNA methylation-regulated APA during the response to cell stress. We find that within the first several hours following exposure to stress, dynamic changes occur within the 3 regulatory region associated with APA of the candidate gene DNAJB6. Our results suggest that targeted DNA-demethylation occurs in a temporal manner following stress, promoting the expression of the DNAJB6 isoform associated with cytosolic chaperone activity. Furthermore, Hi-C data suggests that chromatin structural changes during stress are more widespread than previously appreciated.