Impact of CAR agonist ligand TCPOBOP (27 hr time point) on H3-K27me3 marks in adult male mouse liver
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ABSTRACT:
PROVIDER: PRJNA499052 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8128760_1.fastq.gz | Fastqsanger.gz | |||
| SRR8128760_2.fastq.gz | Fastqsanger.gz | |||
| SRR8128761_1.fastq.gz | Fastqsanger.gz | |||
| SRR8128761_2.fastq.gz | Fastqsanger.gz | |||
| SRR8128762_1.fastq.gz | Fastqsanger.gz |
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Project description:Chromatin immunoprecipitation and sequencing for the H3K27me3 histone mark was performed on livers of male mice either treated with vehicle or with TCPOBOP for 27 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.
2019-06-17 | GSE121914 | GEO
Project description: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.
2019-06-17 | GSE121913 | GEO
Project description:Impact of CAR agonist ligand TCPOBOP (3 hr time point) on H3-K27me3 marks in adult male mouse liver
| PRJNA499053 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. 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.
2019-06-17 | GSE121921 | GEO
Project description:Chromatin immunoprecipitation and sequencing for three transcription factors (RXRa, CEBPa, CEBPb) was performed on livers of male mice treated with vehicle or with TCPOBOP for either 3 h or 27 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.
2019-06-17 | GSE121915 | GEO
Project description:Impact of CAR agonist ligand TCPOBOP (3h and 27hr time points) on H3-K27me3 marks in adult male mouse liver
| PRJNA499062 | ENA
Project description:Impact of CAR agonist ligand TCPOBOP on transcription factor binding in adult male mouse liver
| PRJNA499057 | ENA
Project description:PolyA-selected RNA was isolated from the nuclear fraction of frozen liver tissue from adult male and female ICR/CD1 mice that were treated with a TCPOBOP delivered using either a Low Corn Oil vehice or a High Corn Oil vehicle regimen. Livers were collected and nuclear RNA purified and analyzed either 2 week or 8 weeks after initiating TCPOBOP treatment. These samples are part of a study designed to elucidate genes and gene-based mechanisms underlying TCPOBOP-disrupted liver metabolic dysfunction, including the pericentral steatosis seen within 2 weeks of the initial TCPOBOP exposure. Major findings of this work included the following: Early (1-day) TCPOBOP transcriptional responses were enriched for CAR-bound primary response genes, and for lipogenesis and xenobiotic metabolism and oxidative stress protection pathways; late (2-wk) TCPOBOP responses included many CAR binding-independent secondary response genes, with enrichment for macrophage activation, immune response and cytokine and reactive oxygen species production. Late upstream regulators specific to TCPOBOP-exposed male liver were linked to pro-inflammatory responses and hepatocellular carcinoma progression. TCPOBOP administered weekly to male mice using a high corn oil vehicle activated carbohydrate-responsive transcription factor (MLXIPL)-regulated target genes, dysregulated mitochondrial respiratory and translation regulatory pathways, and induced more advanced liver pathology. Overall, TCPOBOP exposure recapitulated histological and gene expression changes characteristic of emerging steatotic liver disease, including secondary gene responses in liver non-parenchymal cells indicative of transition to a more advanced disease state.
2024-04-07 | GSE248858 | GEO
Project description:Massively parallel reporter assays are widely used to discover functional enhancers but have largely been limited to transfected cell models, which are confounded by vector-induced innate immune responses and lack the physiologically relevant cellular and endogenous hormonal context and chromatin environment of complex mammalian tissues. Here, we combine hydrodynamic injection with a modified STARR-seq-based MPRA to determine condition-specific enhancer activity in mouse liver at scale. Strong liver enhancer activity was observed with STARR-seq libraries containing an Albumin minimal promoter but not when using a Super Core promoter or an origin of replication promoter. We prepared a focused STARR-seq library comprised of 100 PCR-amplified open chromatin regions nearby genes showing sex-biased expression or responsiveness to TCPOBOP, a xenobiotic and agonist ligand of the nuclear receptor CAR (Nr1i3). We assayed STARR-seq activity for the 100 genomic regions in male liver, in female liver and in TCPOBOP-treated male liver to quantitatively measure their intrinsic transcriptional activity under the 3 indicated biological conditions, and thereby identified enhancers whose activity is sex-dependent or xenobiotic-responsive.
2024-06-17 | GSE267041 | GEO
Project description:This work is part of a larger study where we investigated activation of the nuclear receptor and transcription factor CAR (Nr1i3) by its specific agonist ligand TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene), which dysregulates hundreds of genes in mouse liver and is linked to male-biased hepatocarcinogenesis. We used DNase-seq and DNase hypersensitivity site (DHS) analysis to identify several thousand genomic regions (∆DHS) where short-term exposure to TCPOBOP induces localized changes (increases or decreases) in mouse liver chromatin accessibility, many of which cluster together with TCPOBOP-responsive genes. Sites of chromatin opening were highly enriched nearby genes induced by TCPOBOP and chromatin closing was highly enriched nearby genes repressed by TCPOBOP, consistent with TCPOBOP-responsive ∆DHS serving as enhancers and promoters that positively regulate CAR-responsive genes. Gene expression changes lagged behind chromatin opening or closing for a subset of TCPOBOP-responsive ∆DHS. DHS that were specifically responsive to TCPOBOP in male liver were significantly enriched for genomic regions with a basal male bias in chromatin accessibility; however, the male-biased response of hepatocellular carcinoma-related genes to TCPOBOP was not associated with a correspondingly male-biased ∆DHS response. These studies elucidate the genome-wide organization of CAR-responsive genes and of the thousands of associated genomic sites where TCPOBOP exposure induces both rapid and persistent changes in chromatin accessibility.
2018-04-09 | GSE104061 | GEO