GSE121913
Impact of CAR agonist ligand TCPOBOP (3 hr time point) on H3-K27me3 marks in adult male mouse liver
Chromatin immunoprecipitation and sequencing for the H3K27me3 histone mark was performed on livers of male mice either treated with vehicle or with TCPOBOP for 3 h. This dataset is part of a larger study, entitled “Widespread epigenetic changes to the enhancer landscape of mouse liver induced by a specific xenobiotic agonist ligand of the nuclear receptor CAR”, which found that active enhancer and promoter histone marks induced by TCPOBOP were enriched at opening DNase hypersensitive sites (DHS) and TCPOBOP-inducible genes. Enrichment of CAR binding and CAR motifs was seen at opening DHS and their inducible drug/lipid metabolism gene targets, and at many constitutively open DHS located nearby. TCPOBOP-responsive cell cycle and DNA replication genes co-dependent on MET/EGFR signaling for induction were also enriched for CAR binding. A subset of opening DHS and many closing DHS mapping to TCPOBOP-responsive target genes did not bind CAR, indicating an indirect mechanism for their changes in chromatin accessibility. TCPOBOP-responsive DHS were also enriched for induced binding of RXRA, CEBPA and CEBPB, and for motifs for liver-enriched factors that may contribute to liver-specific transcriptional responses to TCPOBOP exposure. These studies elucidate the enhancer landscape of TCPOBOP-exposed liver and the widespread epigenetic changes that are induced by both direct and indirect mechanisms linked to CAR activation. Overall design: Chromatin was isolated from frozen livers from 7 week old wild-type male mice treated with either vehicle or TCPOBOP. Sonicated chromatin from 3-4 individual livers from each group was immunoprecipitated with the following antibody:  H3K27me3 (Abcam Cat # ab6002, 2 µg antibody per 10 µg of sonicated chromatin). This sequencing data set was generated from long DNA fragments (between 600 - 1100 bp) which were digested down to a size of 500 bp and then sequenced.