Feminization of mouse liver gene expression by constitutively active STAT5b
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA803227 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17867538_1.fastq.gz | Fastqsanger.gz | |||
| SRR17867538_2.fastq.gz | Fastqsanger.gz | |||
| SRR17867539_1.fastq.gz | Fastqsanger.gz | |||
| SRR17867539_2.fastq.gz | Fastqsanger.gz | |||
| SRR17867540_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. This SuperSeries is part of a study entitled 'Constitutively active STAT5b feminizes mouse liver gene expression', where delivery of constitutively active STAT5 (STAT5CA) to male mouse liver was shown to induce widespread feminization of the liver, with extensive induction of female-biased genes and repression of male-biased genes, largely mimicking results obtained when male mice are given GH as a continuous infusion. Many of the STAT5CA-responding genes were associated with nearby (< 50 kb) sites of STAT5 binding to liver chromatin, supporting the proposed direct role of persistently active STAT5 in continuous GH-induced liver feminization. The feminizing effects of STAT5CA were dose-dependent; moreover, at higher levels, STAT5CA overexpression resulted in some histopathology, including hepatocyte hyperplasia, and increased karyomegaly and multinuclear hepatocytes. Together, these findings establish that the persistent activation of STAT5 by GH that characterizes female liver is by itself sufficient to account for the sex-dependent expression of a majority of hepatic sex-biased genes.
2022-04-04 | GSE196086 | GEO
Project description:PolyA-selected nuclear RNA isolated from livers of adult male mice administered AAV8-STAT5ca was analyzed by RNA-seq to determine the impact of constitutive STAT5 activation on the expression of sex-biased genes in male mouse liver. This is part of a study entitled 'Constitutively active STAT5b feminizes mouse liver gene expression', where delivery of constitutively active STAT5 (STAT5CA) to male mouse liver was shown to induce widespread feminization of the liver, with extensive induction of female-biased genes and repression of male-biased genes, largely mimicking results obtained when male mice are given GH as a continuous infusion. Many of the STAT5CA-responding genes were associated with nearby (< 50 kb) sites of STAT5 binding to liver chromatin, supporting the proposed direct role of persistently active STAT5 in continuous GH-induced liver feminization. The feminizing effects of STAT5CA were dose-dependent; moreover, at higher levels, STAT5CA overexpression resulted in some histopathology, including hepatocyte hyperplasia, and increased karyomegaly and multinuclear hepatocytes. Together, these findings establish that the persistent activation of STAT5 by GH that characterizes female liver is by itself sufficient to account for the sex-dependent expression of a majority of hepatic sex-biased genes.
2022-04-04 | GSE196015 | GEO
Project description:PolyA-selected total RNA isolated from livers of adult male mice administered AAV8-STAT5ca was analyzed by RNA-seq to determine the impact of constitutive STAT5 activation on the expression of sex-biased genes in male mouse liver. This is part of a study entitled 'Constitutively active STAT5b feminizes mouse liver gene expression', where delivery of constitutively active STAT5 (STAT5CA) to male mouse liver was shown to induce widespread feminization of the liver, with extensive induction of female-biased genes and repression of male-biased genes, largely mimicking results obtained when male mice are given GH as a continuous infusion. Many of the STAT5CA-responding genes were associated with nearby (< 50 kb) sites of STAT5 binding to liver chromatin, supporting the proposed direct role of persistently active STAT5 in continuous GH-induced liver feminization. The feminizing effects of STAT5CA were dose-dependent; moreover, at higher levels, STAT5CA overexpression resulted in some histopathology, including hepatocyte hyperplasia, and increased karyomegaly and multinuclear hepatocytes. Together, these findings establish that the persistent activation of STAT5 by GH that characterizes female liver is by itself sufficient to account for the sex-dependent expression of a majority of hepatic sex-biased genes.
2022-04-04 | GSE196014 | GEO
Project description:STAT5 is an essential transcriptional regulator of the sex-biased actions of GH in the liver. Delivery of constitutively active STAT5 (STAT5CA) to male mouse liver using an engineered adeno-associated virus with high tropism for the liver is shown to induce widespread feminization of the liver, with extensive induction of female-biased genes and repression of male-biased genes, largely mimicking results obtained when male mice are given GH as a continuous infusion. Many of the STAT5CA-responding genes were associated with nearby (< 50 kb) sites of STAT5 binding to liver chromatin, supporting the proposed direct role of persistently active STAT5 in continuous GH-induced liver feminization. The feminizing effects of STAT5CA were dose-dependent; moreover, at higher levels, STAT5CA overexpression resulted in some histopathology, including hepatocyte hyperplasia, and increased karyomegaly and multinuclear hepatocytes. These findings establish that the persistent activation of STAT5 by GH that characterizes female liver is by itself sufficient to account for the sex-dependent expression of a majority of hepatic sex-biased genes. Moreover, histological changes seen when STAT5CA is overexpressed highlight the importance of carefully evaluating such effects before considering STAT5 derivatives for therapeutic use in treating liver disease.
| S-EPMC9070516 | biostudies-literature
Project description:Activation of hepatic NF-kB signaling induces inflammation and ultimately fibrosis. To investigate the underlying mechanism, we used microarrays to detail the global programme of gene expression which is regulated by hepatic NF-kB signaling. We generated transgenic mice which express a constitutively active IKK2 controlled under the LAP promotor. The liver samples were collected from transgenic mice as well as from control animals at the age of 4 weeks. RNA extraction was performed from these liver samples and hybridized on Affymetrix microarrays.
2012-03-31 | E-GEOD-28085 | biostudies-arrayexpress
Project description:A series of dual-channel gene expression profiles obtained using Rosetta/Merck Mouse TOE 75k microarrays was used to examine the sex-dependent and STAT5b-dependent differences in gene expression in adult mouse liver. This series is comprised of 4 pools of 3 randomly chosen independent wildtype male and female mouse liver cDNA samples and 4 pools of 3 randomly chosen independent STAT5b-deficient male and female mouse liver cDNA samples, totaling 16 pools. The pools were paired randomly to generate 4 comparisons of M-WT:F-WT, M-WT:M-KO, F-KO:F-WT, and F-KO:M-KO. Comparison of the set of sex-dependent genes with the set of genes responsive to the loss of STAT5b in males shows that 75% of the sex-specific genes were also regulated by STAT5b in males. Only 20% of the sex-specific genes retained sex-specificity in the absence of STAT5b, indicating a large role for STAT5b in sex-specific liver gene expression. Keywords: genetic knockout and sex response
2006-07-26 | GSE5072 | GEO
Project description:Constitutively Active YAP/TAZ Target Genes
| PRJNA489431 | ENA
Project description:A series of dual-channel gene expression profiles obtained using Rosetta/Merck Mouse TOE 75k microarrays was used to examine the sex-dependent and STAT5b-dependent differences in gene expression in adult mouse liver. This series is comprised of 4 pools of 3 randomly chosen independent wildtype male and female mouse liver cDNA samples and 4 pools of 3 randomly chosen independent STAT5b-deficient male and female mouse liver cDNA samples, totaling 16 pools. The pools were paired randomly to generate 4 comparisons of M-WT:F-WT, M-WT:M-KO, F-KO:F-WT, and F-KO:M-KO. Comparison of the set of sex-dependent genes with the set of genes responsive to the loss of STAT5b in males shows that 75% of the sex-specific genes were also regulated by STAT5b in males. Only 20% of the sex-specific genes retained sex-specificity in the absence of STAT5b, indicating a large role for STAT5b in sex-specific liver gene expression. A pool of cDNA from 3 mice is Cy3-labeled and compared to another pool of cDNA from 3 mice that is Cy5-labeled. The pools are then dye-swapped and compared again. The two pairs of data are averaged together, the averages are normalized across the fluorescent reverse pairings, and the log2 value is reported for each average as well as the anti-log. This is replicated 3 times with independent pools of cDNA for each pair of conditions being compared. There are a total of 4 pairs of conditions compared for a grand total of 12 samples.
2010-07-01 | E-GEOD-5072 | biostudies-arrayexpress
Project description:In several cancer types, STAT (Signal transducer and activator of transcription) transcription factors are constitutively activated. We previously identified a target gene, LPP/miR-28 (LIM domain containing preferred translocation partner in lipoma), induced by constitutive activation of STAT5, but not by transient cytokine-activated STAT5. Here, we demonstrate in transformed hematopoietic cells that binding of both STAT5B and p53 to chromatin is required for transcriptional activity of an alternative LPP/miR-28 promoter. Using a genome-wide approach, we identified 463 genomic positions at promoter regions where STAT5B and p53 are co-localized on the chromatin. At these positions, p53 chromatin binding is dependent on persistent STAT5B activation. The transcriptional activity of selected promoters bound by STAT5B and p53 was significantly changed upon STAT5 or p53 inhibition, and the transcription of these target genes is frequently altered in platelets of myeloproliferative neoplasm patients harboring mutations constitutively activating STAT5. These data suggest that the constitutive STAT5 activation recruits p53 in cancer cells and thereby activates oncogenic transcriptional programs. STAT5B and p53 ChIP-chip with or without JAK2 inhibition (ruxolitinib) to inhibit STAT5 phosphorylation and DNA binding.
2014-02-01 | E-GEOD-38143 | biostudies-arrayexpress
Project description:In several cancer types, STAT (Signal transducer and activator of transcription) transcription factors are constitutively activated. We previously identified a target gene, LPP/miR-28 (LIM domain containing preferred translocation partner in lipoma), induced by constitutive activation of STAT5, but not by transient cytokine-activated STAT5. Here, we demonstrate in transformed hematopoietic cells that binding of both STAT5B and p53 to chromatin is required for transcriptional activity of an alternative LPP/miR-28 promoter. Using a genome-wide approach, we identified 463 genomic positions at promoter regions where STAT5B and p53 are co-localized on the chromatin. At these positions, p53 chromatin binding is dependent on persistent STAT5B activation. The transcriptional activity of selected promoters bound by STAT5B and p53 was significantly changed upon STAT5 or p53 inhibition, and the transcription of these target genes is frequently altered in platelets of myeloproliferative neoplasm patients harboring mutations constitutively activating STAT5. These data suggest that the constitutive STAT5 activation recruits p53 in cancer cells and thereby activates oncogenic transcriptional programs.
2014-02-01 | GSE38143 | GEO