Binding of Drug-Activated CAR/Nr1i3 Alters Metabolic Regulation in the Liver.

ABSTRACT: The constitutive androstane receptor (CAR/Nr1i3) regulates detoxification of drugs and other xenobiotics by the liver. Binding of these compounds, activating ligands, causes CAR to translocate to the nucleus and stimulate genes of detoxification. However, CAR activation also changes metabolism and induces rapid liver growth. To explain this gene regulation, we characterized the genome-wide early binding of CAR; its binding partner, RXRα; and the acetylation that they induced on H4K5. CAR-linked genes showed either stimulation or inhibition and regulated lipid, carbohydrate, and energy metabolism, as well as detoxification. Stimulation of expression increased, but inhibition did not decrease, H4K5Ac. Transcriptional inhibition occurred when CAR bound with HNF4α, PPARα, or FXR on the same en

SUBMITTER: Tian J 

PROVIDER: S-EPMC6222290 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature