Open Chromatin Profiling in Mice Livers Reveals Unique Chromatin Variations Induced by High Fat Diet

Background: Metabolic diseases result from a combination of multiple genetic and environmental factors. Results: High fat diet leads to chromatin remodeling in mice liver tissue in a strain-dependent manner. Conclusion: Diet can induce changes in the epigenome thereby contributing to metabolic disease. Significance: Environmental factors can contribute to complex disease progression through modifications to chromatin. Metabolic diseases result from multiple genetic and environmental factors. We report here that one manner in which environmental factors can contribute to metabolic disease progression is through modification to chromatin. We demonstrate that high fat diet leads to chromatin remodeling in the livers of C57BL/6J mice, as compared with mice fed a control diet, and that these chromatin changes are associated with changes in gene expression. We further show that the regions of greatest variation in chromatin accessibility are targeted by liver transcription factors, including HNF4, CCAAT/enhancer-binding protein (CEBP/), and FOXA1. Repeating the chromatin and gene expression profiling in another mouse strain, DBA/2J, revealed that the regions of greatest chromatin change are largely strain-specific and that integration of chromatin, gene expression, and genetic data can be used to characterize regulatory regions. Our data indicate dramatic changes in the epigenome due to diet and demonstrate strain-specific dynamics in chromatin remodeling.