MicroRNA down-regulation and noise regulation
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No sample metadata fields
View SamplesThe processing of 3' untranslated regions of messenger RNAs changes widely in relation to the cellular state, yet the key regulators remain largely unknown. To uncover sequence elements that drive the choice of polyadenylation (poly(A)) sites in specific conditions, we have developed KAPAC, a method to infer activities of oligomeric sequence motifs on polyadenylation site choice. We demonstrate that KAPAC readily uncovers the sequence elements, targets and binding site position-dependent activity of the mammalian cleavage factor I which regulates the length of 3' untranslated regions.
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Sex, Specimen part, Cell line, Treatment
View SamplesThis project aims to discover canonical gene fusion events from mixed human tissue cell lines.
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View SamplesTo characterize gene response in RPE65-/- mouse model of Lebers congenital amaurosis during progression of the disease, we analyzed differential gene expression in retinae early in the development of the disease, namely before and at the onset of photoreceptor cell death in knock-out mice of 2, 4 and 6 months of age.
Biological characterization of gene response in Rpe65-/- mouse model of Leber's congenital amaurosis during progression of the disease.
Age, Specimen part
View SamplesThis study was designed to identify gene expression changes in skeletal muscle that could define reliably the degree of the severity of Amyotrophic lateral sclerosis (ALS). All samples were from human biopsies, either from healthy muscles or from muscle whose patients were clearly diagnosed as having Amyotrophic Lateral Sclerosis (ALS)
Muscle Gene Expression Is a Marker of Amyotrophic Lateral Sclerosis Severity
Sex, Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Specimen part, Treatment
View SamplesThe kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor coactivator 1 (PGC-1) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1 is a central transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1 in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1 seems largely dispensable for basal renal physiology. However, the central role of PGC-1 in renal mitochondrial biogenesis indicates that activation of PGC-1 in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction.
No associated publication
Specimen part
View SamplesThe peroxisome proliferator-activated receptor c coactivator 1 (PGC-1) proteins are key regulators of cellular bioenergetics and are accordingly expressed in tissues with a high energetic demand. For example, PGC-1a and PGC-1b control organ function of brown adipose tissue, heart, brain, liver and skeletal muscle. Surprisingly, despite their prominent role in the control of mitochondrial biogenesis and oxidative metabolism, expression and function of the PGC-1 coactivators in the retina, an organ with one of the highest energy demands per tissue weight, are completely unknown. Moreover, the molecular mechanisms that coordinate energy production with repair processes in the damaged retina remain enigmatic. In the present study, we thus investigated the expression and function of the PGC-1 coactivators in the healthy and the damaged retina. We show that PGC-1a and PGC-1b are found at high levels in different structures of the mouse retina, most prominently in the photoreceptors. Furthermore, PGC-1a knockout mice suffer from a striking deterioration in retinal morphology and function upon detrimental light exposure. Gene expression studies revealed dysregulation of all major pathways involved in retinal damage and apoptosis, repair and renewal in the PGC-1a knockouts. The light-induced increase in apoptosis in vivo in the absence of PGC-1a was substantiated in vitro, where overexpression of PGC-1a evoked strong anti-apoptotic effects. Finally, we found that retinal levels of PGC-1 expression are reduced in different mouse models for retinitis pigmentosa. We demonstrate that PGC-1a is a central coordinator of energy production and, importantly, all of the major processes involved in retinal damage and subsequent repair. Together with the observed dysregulation of PGC-1a and PGC-1b in retinitis pigmentosa mouse models, these findings thus imply that PGC-1a might be an attractive target for therapeutic approaches aimed at retinal degeneration diseases.
No associated publication
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.
Specimen part
View SamplesSkeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor coactivator 1 (PGC-1), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1 and gene expression upon PGC-1 over-expression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto underestimated number of transcription factor partners involved in mediating PGC-1 action. In particular, principal component analysis of TFBSs at PGC-1 binding regions predicts that, besides the well-known role of the estrogen-related receptor (ERR), the activator protein-1 complex (AP-1) plays a major role in regulating the PGC-1-controlled gene program of hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1.
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Treatment
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