Abstract


Many xenobiotics are metabolized in mammalian liver by pathways regulated by constitutive androstane receptor (CAR). Here, we identify early gene targets of mouse liver CAR and investigate their associated, CAR-induced changes in local chromatin accessibility, histone modifications and transcription factor (TF) recruitment. Genes induced or repressed by the CAR agonist TCPOBOP were identified by RNA-Seq after 3 or 27 hr. Chromatin sites that dynamically open or close following CAR activation (changes in DNase I hypersensitive sites, ΔDHS) were identified by DNase-Seq. view more

Many xenobiotics are metabolized in mammalian liver by pathways regulated by constitutive androstane receptor (CAR). Here, we identify early gene targets of mouse liver CAR and investigate their associated, CAR-induced changes in local chromatin accessibility, histone modifications and transcription factor (TF) recruitment. Genes induced or repressed by the CAR agonist TCPOBOP were identified by RNA-Seq after 3 or 27 hr. Chromatin sites that dynamically open or close following CAR activation (changes in DNase I hypersensitive sites, ΔDHS) were identified by DNase-Seq. DNA regulatory regions that contain the histone marks H3K4me1, H3K27ac and/or H3K27me3 were identified by ChIP-Seq. Genes dysregulated in 3 hr TCPOBOP-treated mouse liver were enriched in KEGG pathways for retinol and drug metabolism (DAVID analysis; p

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