Data from: Widespread epigenetic changes to the enhancer landscape of mouse liver induced by a specific xenobiotic agonist ligand of the nuclear receptor CAR
Data files
Jun 19, 2019 version files 104.66 MB
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Supplemental_Figs_S1_to_S13_Rampersaud_ToxSci_2019.pdf
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Table_S1_Rampersaud_ToxSci_2019_.xlsx
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Table_S2AB_Rampersaud_ToxSci_2019.xlsx
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Table_S2CDE_Rampersaud_ToxSci_2019.xlsx
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Table_S2FGHI_Rampersaud_ToxSci_2019_.xlsx
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Table_S3_Rampersaud_ToxSci_2019.xlsx
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Table_S4_Rampersaud_ToxSci_2019.xlsx
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Table_S5_Rampersaud_ToxSci_2019.xlsx
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Table_S6_Rampersaud_ToxSci_2019.xlsx
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Jun 19, 2019 version files 209.33 MB
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Supplemental_Figs_S1_to_S13_Rampersaud_ToxSci_2019.pdf
8.09 MB
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Table_S1_Rampersaud_ToxSci_2019_.xlsx
23.23 MB
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Table_S2AB_Rampersaud_ToxSci_2019.xlsx
15.07 MB
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Table_S2CDE_Rampersaud_ToxSci_2019.xlsx
16.34 MB
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Table_S2FGHI_Rampersaud_ToxSci_2019_.xlsx
6 MB
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Table_S3_Rampersaud_ToxSci_2019.xlsx
8.28 MB
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Table_S4_Rampersaud_ToxSci_2019.xlsx
17.26 MB
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Table_S5_Rampersaud_ToxSci_2019.xlsx
10.11 MB
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Table_S6_Rampersaud_ToxSci_2019.xlsx
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Abstract
CAR (Nr1i3), a liver nuclear receptor and xenobiotic sensor, induces drug, steroid and lipid metabolism and dysregulates genes linked to hepatocellular carcinogenesis, but its impact on the liver epigenome is poorly understood. TCPOBOP, a halogenated xenochemical and highly specific CAR agonist ligand, induces localized chromatin opening or closing at several thousand mouse liver genomic regions, discovered as differential DNase-hypersensitive sites (ΔDHS). Active enhancer and promoter histone marks induced by TCPOBOP were enriched at opening 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. The global maps of thousands of environmental chemical-induced epigenetic changes described here constitute a rich resource for further research on xenochemical effects on liver chromatin states and the epigenome.