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RNA-seq gene expression profiling determined for five subcellular fractions for protein coding and lncRNA genes from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE160722 | GEO | 2021/03/01

REPOSITORIES: GEO

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Impact of CAR Agonist Ligand TCPOBOP on Mouse Liver Chromatin Accessibility.

Project description: Not available

| S-EPMC6016691 | biostudies-literature

STARR-seq library profiling 100 defined open chromatin regions (‘focused library’) in livers of male and female mice treated with the nuclear receptor CAR (Nr1i3) agonist ligand TCPOBOP.

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

RNA-seq gene expression profiling determined for five subcellular fractions for protein coding and lncRNA genes from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand

Project description:RNA-seq gene expression profiling determined for five subcellular fractions for protein coding and lncRNA genes from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand

| PRJNA674064 | ENA

Global STARR-seq library profiling of open chromatin regions in livers of mice treated with the nuclear receptor CAR (Nr1i3) agonist ligand TCPOBOP, in livers of control male mice and in livers of control female mice. [G187_global]

Project description:Massively parallel reporter assays (MPRA) 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. Analysis of a global STARR-seq library, comprised of ~50,000 genomic sequences released by DNase-I digestion of mouse liver nuclei, identified condition-specific enhancers and revealed strong correlations between liver enhancer activity and the chromatin state of the corresponding endogenous genomic regions.

2024-06-17 | GSE267046 | GEO

RNA-seq gene expression profiling of RefSeq genes in nuclear RNA from livers of mice treated with the nuclear receptor CAR (Nr1i3) agonist ligand TCPOBOP for 2 week or for 8 week.

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

RNA-seq gene expression profiling of protein coding and lncRNA genes in nucleoplasmic RNA from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand [G176]

Project description:PolyA-selected RNA was isolated from the nucleoplasmic fraction of frozen liver tissue from adult male and female ICR/CD1 mice that were treated with 3 mg/kg TCPOBOP disolved in corn oil, or corn oil vehicle, for 27 hr. These samples are part of a study where we characterize global patterns of expression, maturation and localization for both lncRNA and protein coding gene transcripts in mouse liver, and where we identify candidate regulatory lncRNAs that may be important for a variety of hepatic functions, based on their co-localized within topologically associating domains, or their transcription divergent, antisense or intergenic to protein coding genes associated with key pathways linked to hepatic physiology and disease.

2021-03-01 | GSE160718 | GEO

RNA-seq gene expression profiling of protein coding and lncRNA genes in nuclear RNA from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand [G175]

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 3 mg/kg TCPOBOP disolved in corn oil, or corn oil vehicle, for 27 hr. These samples are part of a study where we characterize global patterns of expression, maturation and localization for both lncRNA and protein coding gene transcripts in mouse liver, and where we identify candidate regulatory lncRNAs that may be important for a variety of hepatic functions, based on their co-localized within topologically associating domains, or their transcription divergent, antisense or intergenic to protein coding genes associated with key pathways linked to hepatic physiology and disease.

2021-03-01 | GSE160716 | GEO

RNA-seq gene expression profiling of protein coding and lncRNA genes in cytoplasmic RNA from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand [G174]

Project description:PolyA-selected RNA was isolated from the cytoplasmic fraction of frozen liver tissue from adult male and female ICR/CD1 mice that were treated with 3 mg/kg TCPOBOP disolved in corn oil, or corn oil vehicle, for 27 hr. These samples are part of a study where we characterize global patterns of expression, maturation and localization for both lncRNA and protein coding gene transcripts in mouse liver, and where we identify candidate regulatory lncRNAs that may be important for a variety of hepatic functions, based on their co-localized within topologically associating domains, or their transcription divergent, antisense or intergenic to protein coding genes associated with key pathways linked to hepatic physiology and disease.

2021-03-01 | GSE160712 | GEO

RNA-seq gene expression profiling of protein coding and lncRNA genes in chromatin-bound RNA from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand [G178]

Project description:PolyA-selected RNA was isolated from the chromatin bound fraction of frozen liver tissue from adult male and female ICR/CD1 mice that were treated with 3 mg/kg TCPOBOP disolved in corn oil, or corn oil vehicle, for 27 hr. These samples are part of a study where we characterize global patterns of expression, maturation and localization for both lncRNA and protein coding gene transcripts in mouse liver, and where we identify candidate regulatory lncRNAs that may be important for a variety of hepatic functions, based on their co-localized within topologically associating domains, or their transcription divergent, antisense or intergenic to protein coding genes associated with key pathways linked to hepatic physiology and disease.

2021-03-01 | GSE160720 | GEO

Impact of CAR agonist ligand TCPOBOP on transcription factor binding in adult male mouse liver

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

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