Effect of hepatic FBXL5 deficiency on the chromatin accessibility in hepatocytes during cholestasis

Aberrant iron metabolism is considered to be a risk factor for the exacerbation of chronic liver disease. Recently, increasing evidence points out the contribution of iron to epigenetic regulation in several biological contexts. However, the involvement of iron-mediated epigenetic regulation in the progression of chronic liver disease is unknown. To investigate the impact of iron on hepatocyte epigenetics during the progression of chronic liver disease, mice with genetic iron overload in the liver (Alb-Cre/FBXL5F/F) were fed with a cholestasis-inducing diet (0.1% DDC diet). Hepatocytes were isolated from the diseased livers of Alb-Cre/FBXL5F/F and FBXL5F/F mice and subjected to ATAC-seq. Chromatin accessibility of several genes including chemokines was altered in hepatocytes of Alb-Cre/FBXL5F/F mice in comparison to those of FBXL5F/F mice, suggesting that iron participates in the fine-tuning of hepatocyte epigenetics in chronic liver disease.