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Profiling ERRb-target genes in mouse ES cells

ABSTRACT: We found ERRb activates the transcription through two molecular pathways, which are interaction to AF2-region binding PGC-1a/cofactors and general transcription factor TFIIH. To analyze the significance of these pathways in cells, we first identified ERRb-target genes in ES cells. Estrogen-related receptors (ERRa/b/g) are orphan nuclear receptors that function in a number of energy-demanding physiological processes, as well as in development and stem cell maintenance, but mechanisms underlying target gene activation are largely unknown. Here, reconstituted biochemical assays that manifest ERR-dependent transcription have revealed two complementary mechanisms. On chromatin templates ERR-dependent transcription is dependent on interactions with cell-specific coactivator PGC-1a, which in turn recruits the ubiquitous p300 and MED1/Mediator coactivators. The N-terminal half of PGC-1a is necessary and sufficient for these interactions and for transcription both in vitro and in vivo. On DNA templates, ERRs activate transcription with just the normal complement of general initiation factors in a manner dependent upon interaction of the ERR DNA-binding domain with the p52 subunit of initiation factor TFIIH. Importantly, the PGC-1a and TFIIH interactions are both essential for ERRb/g functions in maintaining embryonic stem cell pluripotency through regulation of target gene transcription.

ORGANISM(S): Mus musculus

PROVIDER: GSE164633 | GEO | 2022/12/31

REPOSITORIES: GEO

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Effect of deletion of ERRalpha, ERRbeta and/or ERRgamma on gene expression in soleus and extensor digitorum longus (EDL) skeletal muscles

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2023-01-09 | GSE214876 | GEO

Project description:Background: A gradual decline in renal function occurs even in healthy aging individuals. In addition to aging per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction and inflammation, which collectively contribute to age-related kidney dysfunction and disease. Here we studied the role of the nuclear hormone receptors, the estrogen related receptors (ERRs) in regulation of age-related mitochondrial dysfunction and inflammation. Methods: ERRs were decreased in aging human and mouse kidneys and were preserved in aging mice with lifelong caloric restriction (CR). Pan-ERR agonist was used to treat 21-month-old mice for 8-weeks. Results: Remarkably, only an 8-week treatment with the pan-ERR agonist reversed the age-related increases in albuminuria and podocyte loss, mitochondrial dysfunction and inflammatory cytokines, including the cGAS-STING and STAT3 signaling pathways. A 3-week treatment of 21-month-old mice with a STING inhibitor reversed the increases in inflammatory cytokines and the senescence marker p21 but also unexpectedly reversed the age-related decreases in PGC-1α, ERRα, mitochondrial complexes and MCAD expression. Conclusions: Our studies identified ERRs as important modulators of age-related mitochondrial dysfunction and inflammation.

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ERR agonism reverses mitochondrial dysfunction and inflammation in the aging kidney

Project description:A gradual decline in renal function occurs even in healthy aging individuals. In addition to aging per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction, and inflammation, which collectively contribute to age-related kidney disease. Here we studied the role of the nuclear hormone receptors, the estrogen related receptors (ERRs) in regulation of age-related mitochondrial dysfunction and inflammation. ERRs are decreased in aging human and mouse kidneys and preserved in aging mice with lifelong caloric restriction (CR). Our studies identified ERRs as important modulators of age-related mitochondrial dysfunction and inflammation. ERRα, ERRβ, and ERRγ levels are decreased in the aging kidney. Remarkably, only a 4-week treatment of 21-month-old mice with the pan ERR agonist reversed the age-related increases in albuminuria and podocyte loss, mitochondrial dysfunction and inflammatory cytokines, including the cGAS-STING and STAT3 signaling pathways. A 3-week treatment of 21-month-old mice with a STING inhibitor reversed the increases in inflammatory cytokines and the senescence marker p21 but also unexpectedly reversed the age-related decreases in PGC-1α, ERRα, mitochondrial complexes and Mcad expression.

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2022-12-31 | GSE196202 | GEO

Gene Expression Profiling of PGC-1a KO mouse striata

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2008-06-14 | E-GEOD-5968 | biostudies-arrayexpress

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2014-01-13 | E-GEOD-43798 | biostudies-arrayexpress

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