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.
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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): synthetic construct Mus musculus
PROVIDER: GSE267041 | GEO | 2024/06/17
REPOSITORIES: GEO
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