Transcriptome comparison between WT and GPS2 liver knockout (LKO) livers and GPS2 NCOR PPARa cistrome and epigenome analysis in livers.
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ABSTRACT:
PROVIDER: PRJNA450317 | ENA |
REPOSITORIES: ENA
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Project description:Obesity-associated lipid overload triggers non-alcoholic fatty liver diseases (NAFLD), which in part may be driven by alterations of regulatory transcription networks and hepatocyte-selective epigenomes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR)/ histone deacetylase 3 (HDAC3) complex, is a central component of such networks and accelerates the progression of non-alcoholic steatohepatitis (NASH). In hepatocyte-specific Gps2 knockout mice, loss of GPS2 alleviated the development of diet-induced steatosis and fibrosis and caused activation of lipid catabolic genes. By determining differential cistromes, epigenomes and transcriptomes in wild-type, single and double knockout mice, we identified the lipid-sensing nuclear receptor PPARa as a direct target of GPS2. We also provide evidence that in hepatocytes, unlike in macrophages, GPS2 acts in concert with the NCOR subunit of the corepressor complex. By analyzing the liver transcriptomes of human patients, we found that GPS2 expression positively correlated with the expression of NASH/fibrosis signature genes. Collectively, our data suggest that the GPS2-PPARa partnership in hepatocytes may influence the development of NASH/fibrosis in mice and in humans.
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2016-02-20 | E-GEOD-73298 | biostudies-arrayexpress
Project description:If the function of the nuclear receptor PPARa is well-known during a prolongated fasting, its hepatic biological function during feeding and refeeding conditions still needs to be investigated. Moreover, in vivo data collected so far on PPARa function during fasting were obtained using the total Ppara KO transgenic mouse model. To identify genes whose expression is under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice under three nutritional challenges. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice fed ad libitum, fasted for 24 hours and refed. There are 52 liver samples, each from an individual mouse. The samples are from Ppara liver KO (LKO), Ppara KO (KO), wild-type (WT) and liver WT (LWT) male mice of 8 week-old from the same genetic background (C57Bl/6J) fed ad libitum, fasted for 24 hours, fasted for 24 hours and then refed 24 hours more with glucose added in water (200g/l). In fed condition (Fed), n= 3 mice for LKO, LWT genotypes, n= 5 for KO and n= 4 fot WT; in fasting condition (Fas), n=5 for LKO, LWT and WT genotypes and n= 3 for KO; in refeeding condition (Ref), n= 5 for LKO, KO and WT genotypes and n= 4 for LWT. All mice were sacrified at ZT14.
2016-02-20 | E-GEOD-73299 | biostudies-arrayexpress
Project description:Fenofibrate is a specific agonist of the nuclear receptor PPARa. To identify the gene expression under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice.
2016-02-20 | GSE73298 | GEO
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2008-12-03 | E-GEOD-10001 | biostudies-arrayexpress
Project description:If the function of the nuclear receptor PPARa is well-known during a prolongated fasting, its hepatic biological function during feeding and refeeding conditions still needs to be investigated. Moreover, in vivo data collected so far on PPARa function during fasting were obtained using the total Ppara KO transgenic mouse model. To identify genes whose expression is under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice under three nutritional challenges. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice fed ad libitum, fasted for 24 hours and refed.
2016-02-20 | GSE73299 | GEO
Project description:To identify genes whose expression is under the strict dependence of hepatocyte PPARa activity, we used a mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to their liver WT littermates (albumin-Cre-/- Pparaflox/flox or LWT) fed ad libitum or fasted for 24 hours.
2017-12-16 | GSE96559 | GEO
Project description:Genome-wide profiling of PPARA in PPARA agonist-treated mouse livers [ChIP-seq]
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2022-04-05 | GSE154276 | GEO
Project description:The thyroid hormone receptor (TR) has been proposed to regulate target genes in the absence of triiodothyronine (T3), through the recruitment of the corepressors, NCoR and SMRT. NCoR and SMRT may thus play a key role in both hypothyroidism and resistance to thyroid hormone, though this has never been tested in vivo. To accomplish this we developed mice that express in the liver a NCoR protein (L-NCoR∆ID) that cannot interact with the TR. L-NCoR∆ID mice develop normally, however when made hypothyroid the repression of many positively regulated T3-target genes is abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by the unliganded TR. Remarkably, in the euthyroid state, expression of many T3-targets are also upregulated in L-NCoR∆ID mice, demonstrating that NCoR also determines the magnitude of the response to T3 in euthyroid animals. While positive T3 targets were upregulated in L-NCoR∆ID mice in the hypo and euthyroid state there was less effect seen on negatively regulated T3 target genes. Thus, NCoR is a specific regulator of T3-action in vivo and mediates the activity of the unliganded TR. Furthermore, NCoR may play a key role in determining the differences in individual responses to similar levels of circulating T3. Keywords: NCoR, thyroid hormone signaling, mouse liver, DNA Microarray
2008-12-04 | GSE10001 | GEO