Signal transduction from the extracellular matrix to the arterial wall plays a critical role during development of the vasculature. We now report the discovery of a Myocardin-like Protein (MKL)2/TGF- signaling pathway that is required for maturation and stabilization of the vasculature. Mkl2-/- null embryos exhibit profound derangements in the tunica media leading to aneurismal dilation, dissection and hemorrhage.
Myocardin-like protein 2 regulates TGFβ signaling in embryonic stem cells and the developing vasculature.
Specimen part
View SamplesWe have utilized the RNA-Seq technology to identify genes with distinct expression patterns between failing and non-failing hearts. In an era of next-generation sequencing studies, our study demonstrates how knowledge gained from a small set of samples with accurately measured gene expressions using RNA-Seq can be leveraged as a complementary strategy to discern the genetics of complex disorders. Overall design: Identify the signature genes based on RNA-seq come from six Heart Failure and healthy individuals. Validation is based on Affymetrix microarray of a total of 313 individuals with/without Heart Failure.
MetaDiff: differential isoform expression analysis using random-effects meta-regression.
No sample metadata fields
View SamplesLeft ventricular myocardium was snap-frozen at time of cardiac transplantation from patients with advanced idiopathic or ischemic cardiomyopathy, or at time of harvest from unused donor heart that serve as a nonfailing control. No subjects received mechanical support devices.
Transcriptional genomics associates FOX transcription factors with human heart failure.
No sample metadata fields
View SamplesWe have utilized the RNA-Seq technology to identify genes with distinct expression patterns between failing and non-failing hearts. In an era of next-generation sequencing studies, our study demonstrates how knowledge gained from a small set of samples with accurately measured gene expressions using RNA-Seq can be leveraged as a complementary strategy to discern the genetics of complex disorders.
RNA-Seq identifies novel myocardial gene expression signatures of heart failure.
Sex, Age, Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
BET bromodomains mediate transcriptional pause release in heart failure.
Age, Specimen part, Treatment
View SamplesHeart failure (HF) is driven via interplay between master regulatory transcription factors and dynamic alterations in chromatin structure. While pathologic gene transactivation in this context is known to be associated with recruitment of histone acetyl-transferases and local chromatin hyperacetylation, the role of epigenetic reader proteins in cardiac biology is unknown. We therefore undertook a first study of acetyl-lysine reader proteins, or bromodomains, in HF. Using a chemical genetic approach, we establish a central role for BET-family bromodomain proteins in gene control during HF pathogenesis. BET inhibition potently suppresses cardiomyocyte hypertrophy in vitro and pathologic cardiac remodeling in vivo. Integrative transcriptional and epigenomic analyses reveal that BET proteins function mechanistically as pause-release factors critical to activation of canonical master regulators and effectors that are central to HF pathogenesis and relevant to the pathobiology of failing human hearts. This study implicates epigenetic readers in cardiac biology and identifies BET co-activator proteins as therapeutic targets in HF.
BET bromodomains mediate transcriptional pause release in heart failure.
Specimen part
View SamplesHeart failure (HF) is driven via interplay between master regulatory transcription factors and dynamic alterations in chromatin structure. While pathologic gene transactivation in this context is known to be associated with recruitment of histone acetyl-transferases and local chromatin hyperacetylation, the role of epigenetic reader proteins in cardiac biology is unknown. We therefore undertook a first study of acetyl-lysine reader proteins, or bromodomains, in HF. Using a chemical genetic approach, we establish a central role for BET-family bromodomain proteins in gene control during HF pathogenesis. BET inhibition potently suppresses cardiomyocyte hypertrophy in vitro and pathologic cardiac remodeling in vivo. Integrative transcriptional and epigenomic analyses reveal that BET proteins function mechanistically as pause-release factors critical to activation of canonical master regulators and effectors that are central to HF pathogenesis and relevant to the pathobiology of failing human hearts. This study implicates epigenetic readers in cardiac biology and identifies BET co-activator proteins as therapeutic targets in HF.
BET bromodomains mediate transcriptional pause release in heart failure.
Age, Specimen part
View SamplesAffymetrix Hu133 GeneCHIP Microarray data for Control and c-MYC knock-down (KD) human cancer cell lines.
Novel c-MYC target genes mediate differential effects on cell proliferation and migration.
No sample metadata fields
View SamplesWe implemented an optimized processing, using alternative Chip Description Files (CDFs) and fRMA normalization, which improve the quality of downstream analysis.
Accurate data processing improves the reliability of Affymetrix gene expression profiles from FFPE samples.
Specimen part
View SamplesTreatment with Aurora inhibitors has been shown to induce diverse biological responses in different tumor cell lines, in part depending on their p53 status. To characterize at the transcriptional level the effects of Danusertib we analyzed by microarray different tumor cell lines, with WT or mutant p53 status, that showed differential cell cycle response upon drug treatment.
Transcriptional analysis of the Aurora inhibitor Danusertib leading to biomarker identification in TP53 wild type cells.
Specimen part, Cell line
View Samples