Total RNA was isolated from 3 WT and 3 ERRa null hearts and independent hybridizations were performed using MOE430 2.0 microarrays. Expression profiling was conducted to determine changes in gene expression in hearts lacking ERRa. The expression of genes involved in heart and muscle development, muscle contraction, lipid metabolism, OxPhos, protein metabolism and transcription were affected by the loss of ERRa.
Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma.
Sex, Specimen part
View Samples3 ventricles from E18.5 male mice were pooled for each array. Three arrays per genotype.
ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart.
No sample metadata fields
View SamplesThe canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor represses differentiation. We now identify Barx2,MyoD,and Pax7 as novel components of the Wnt effector complex, providing a new molecular pathway for regulation of muscle progenitor differentiation. Canonical Wnt signaling induces Barx2 expression in muscle progenitors and perturbation of Barx2 leads to misregulation of Wnt target genes. Barx2 activates two endogenous Wnt target promoters as well as the Wnt reporter gene TOPflash, the latter synergistically with MyoD. Moreover, Barx2 interacts with the core Wnt effectors ß-catenin and TCF, is recruited to TCF/LEF sites, and promotes recruitment of ß-catenin. In contrast, Pax7 represses the Wnt reporter gene and antagonizes the activating effect of Barx2. Pax7 also binds ß-catenin suggesting that Barx2 and Pax7 may compete for interaction with the core Wnt effector complex. Overall, the data show for the first time that Barx2, Pax7, and MRFs can act as direct transcriptional effectors of Wnt signals in myoblasts and that Barx2 and Wnt signaling participate in a regulatory loop. We propose that antagonism between Barx2 and Pax7 in regulation of Wnt signaling may help mediate the switch from myoblast proliferation to differentiation. Overall design: RNA-Seq analyses was used to characterize gene expression in primary myoblasts from wild-type and Barx2 knockout mice.
Barx2 and Pax7 have antagonistic functions in regulation of wnt signaling and satellite cell differentiation.
No sample metadata fields
View SamplesCircadian regulation of gene expression in central and peripheral tissue has been studied in mice. The biomedical implications of this findings led us to the development of a model in which to study the circadian mechanisms underlying primate physiology.
Twenty-four-hour rhythmic gene expression in the rhesus macaque adrenal gland.
No sample metadata fields
View SamplesDecreased bile secretion in rodents by either ligation of the common bile duct or induction of cirrhosis causes changes in the small intestine, including bacterial overgrowth and translocation across the mucosal barrier. Oral administration of bile acids inhibits these effects. The genes regulated by FXR in ileum suggested that it might contribute to the enteroprotective actions of bile acids. To test this hypothesis, mice were administered either GW4064 or vehicle for 2 days and then subjected to bile duct ligation (BDL) or sham operation. After 5 days, during which GW4064 or vehicle treatment was continued, the mice were killed and their intestines were analyzed for FXR target gene expression.
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor.
Sex, Treatment
View SamplesObstruction of bile flow results in bacterial proliferation and mucosal injury in the small intestine that can lead to the translocation of bacteria across the epithelial barrier and systemic infection. These adverse effects of biliary obstruction can be inhibited by administration of bile acids. Here we show that the farnesoid X receptor (FXR), a nuclear receptor for bile acids, induces genes involved in enteroprotection and inhibits bacterial overgrowth and mucosal injury in ileum caused by bile duct ligation. Mice lacking FXR have increased ileal levels of bacteria and a compromised epithelial barrier. These findings reveal a central role for FXR in protecting the distal small intestine from bacterial invasion and suggest that FXR agonists may prevent epithelial deterioration and bacterial translocation in patients with impaired bile flow. In this report we have examined the role of FXR in the ileum. We demonstrate that it plays a crucial role in preventing bacterial overgrowth and maintaining the integrity of the intestinal epithelium
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor.
Sex, Compound
View SamplesMetastasis is the major cause of cancer mortality. Up to 25% of early stage sporadic colorectal cancer (CRC) patients succumb to metastasis after curative surgery.
A 'metastasis-prone' signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
AMPK and PPARdelta agonists are exercise mimetics.
No sample metadata fields
View SamplesExercise activates serine/threonine kinase AMPK and transcriptional factor PPARdelta that re-model metabolism and endurance capacity of skeletal muscle. Whether and how synthetic activation of these molecules regulated muscle gene signature is unknown.
AMPK and PPARdelta agonists are exercise mimetics.
No sample metadata fields
View SamplesExercise training increases endurance by inducing global gene expression changes in skeletal muscles. The extent to which the genetic effects of exercise can be mimicked by synthetic drugs is unknown.
AMPK and PPARdelta agonists are exercise mimetics.
No sample metadata fields
View Samples