In vivo genome-wide binding interactions of mouse and human constitutive androstane receptors reveal novel gene targets.

ABSTRACT: The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor orchestrating complex roles in cell and systems biology. Species differences in CAR's effector pathways remain poorly understood, including its role in regulating liver tumor promotion. We developed transgenic mouse models to assess genome-wide binding of mouse and human CAR, following receptor activation in liver with direct ligands and with phenobarbital, an indirect CAR activator. Genomic interaction profiles were integrated with transcriptional and biological pathway analyses. Newly identified CAR target genes included Gdf15 and Foxo3, important regulators of the carcinogenic process. Approximately 1000 genes exhibited differential binding interactions between mouse and human CAR, including the proto-oncogenes, Myc

SUBMITTER: Niu B 

PROVIDER: S-EPMC6144799 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature