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GSE41558
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A major component of the cardiac stress response is the simultaneous activation of several gene regulatory networks. Interestingly, the transcriptional regulator steroid receptor coactivator-2, SRC-2 is often decreased during cardiac failure in humans. We postulated that SRC-2 suppression plays a mechanistic role in the stress response and that SRC-2 activity is an important regulator of the adult heart gene expression profile. Genome-wide microarray analysis, confirmed with targeted gene expression analyses revealed that genetic ablation of SRC-2 activates the fetal gene program in adult mice as manifested by shifts in expression of a) metabolic and b) sarcomeric genes, as well as associated modulating transcription factors. While these gene expression changes were not accompanied by changes in left ventricular weight or cardiac function, imposition of transverse aortic constriction (TAC) predisposed SRC-2 knockout (KO) mice to stress-induced cardiac dysfunction. In addition, SRC-2 KO mice lacked the normal ventricular hypertrophic response as indicated through heart weight, left ventricular wall thickness, and blunted molecular signaling known to activate hypertrophy. Our results indicate that SRC-2 is involved in maintenance of the steady-state adult heart transcriptional profile, with its ablation inducing transcriptional changes that mimic a stressed heart. These results further suggest that SRC-2 deletion interferes with the timing and integration needed to respond efficiently to stress through disruption of metabolic and sarcomeric gene expression and hypertrophic signaling, the three key stress responsive pathways.
Publication Title
SRC-2 coactivator deficiency decreases functional reserve in response to pressure overload of mouse heart.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Increased COUP-TFII levels are found in human dilated cardiomyopathy as well as in mouse models that develop cardiomyopathy. COUP-TFII overexpression in adult mouse hearts caused ventricular dilation and compromised cardiac functions. To gain insights on COUP-TFIIs effect in hearts, we identified the molecular profile of COUP-TFII overexpressing hearts through microarray analysis. The result may shred light on molecular mechanisms that mediate development of dilated cardiomyopathy.
Publication Title
Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The Cdk7/cyclin H/mnage--trois 1 (MAT1) heterotrimer has proposed functions in transcription as the kinase component of basal transcription factor TFIIH and is activated in adult hearts by hypertrophic pathways. Using cardiac-specific Cre, we ablated MAT1 in myocardium. Despite reduced Cdk7 activity, MAT1-deficient hearts grew normally. However, fatal heart failure ensued at 6-8 weeks. By microarray profiling, quantitative RT-PCR, and Western blotting at 4 weeks, genes for energy metabolism were found to be suppressed selectively, including targets of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1). Cardiac metabolic defects were substantiated in isolated perfused hearts and isolated mitochondria. In culture, deleting MAT1 with Cre disrupted PGC-1 function: PGC-1 failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1 was functionally defective, and PGC-1 likewise was deficient. PGC-1 was shown to interact with MAT1 and Cdk7, in co-precipitation assays. Thus, we demonstrate an unforeseen essential role for MAT1 in operation of the PGC-1 family of co-activators.
Publication Title
Ménage-à-trois 1 is critical for the transcriptional function of PPARgamma coactivator 1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We used microarrays to detail the global changes in gene expression resulting from miR-95 overexpression
Publication Title
miRNA-95 mediates radioresistance in tumors by targeting the sphingolipid phosphatase SGPP1.
Sample Metadata Fields
Cell line, Treatment
View Samples- Pan troglodytes, Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U95B Array (hgu95b), Affymetrix Human Genome U95D Array (hgu95d), Affymetrix Human Genome U95 Version 2 Array (hgu95av2), Affymetrix Human Genome U95C Array (hgu95c), Affymetrix Human Genome U95E Array (hgu95e)
Description
Gene expression profiling in brain of three adult humans and three adult chimpanzees
Publication Title
DNA sequence and comparative analysis of chimpanzee chromosome 22.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples