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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.

ABSTRACT: 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.

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE267041 | GEO | 2024/06/17

REPOSITORIES: GEO

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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

STARR-seq enhancer activity determined following hydrodynamic delivery of STARR-seq plasmid library to mouse liver using three different STARR-seq promoters: Super Core promoter, ORI promoter, and minimal Albumin promoter [G173]

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2024-06-17 | GSE267075 | GEO

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

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2019-06-17 | GSE121915 | GEO

Impact of CAR agonist ligand TCPOBOP (27 hr time point) on H3-K27me3 marks in adult male mouse liver

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2019-06-17 | GSE121914 | GEO

Impact of CAR agonist ligand TCPOBOP (3 hr time point) on H3-K27me3 marks in adult male mouse liver

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2019-06-17 | GSE121913 | GEO

Changes in chromatin accessibility in mouse liver following TCPOBOP exposure

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2022-04-25 | GSE188488 | GEO

Modulation of the mouse liver epigenome following TCPOBOP exposure

Project description:Changes in the activating histone-H3 chromatin marks K4me1, K4me3, and K27ac were assayed in male mouse liver following exposure to TCPOBOP, an agonist ligand of the nuclear receptor CAR (constitutive androstane receptor). This work 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" (Tox Sci, 2019).

2020-04-28 | GSE104060 | GEO

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