Identification of m6A-mediated transcriptome changes in mouse liver after exposure to HFD, PCB126 and Aroclor mixtures

Exposure to polychlorinated biphenyls (PCBs) and high fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor (EGFR) signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes. This study tested the hypothesis that PCB exposure alters the global RNA epitranscriptome in HFD-fed male mouse liver. C57BL/6J male mice were fed a 42% milk fat diet (HFD) and exposed to Aroclor 1260 (20mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126, or vehicle control for 12 weeks. RNA modifications altered by PCB exposure were analyzed in comparison to the readers, writers, and erasers of these marks in the RNA transcriptome. Male C57Bl/6J mice were fed a HFD (42% kCal from fat) and treated with Aroclor 1260, PCB 126, and the combination of Aroclor 1260 + PCB 126 for 12 weeks. A total of four sample groups with five replicates each were sequenced (high fat diet alone; high fat diet with Aroclor 1260 treament; high fat diet with PCB 126 treatment; and high fat diet with Aroclor 1260 + PCB 126 treatment).