The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2.
Phosphatidylinositol 3-kinase (PI3K) signaling via glycogen synthase kinase-3 (Gsk-3) regulates DNA methylation of imprinted loci.
Specimen part
View SamplesXBP1 is the transcriptino factor that is activated by the ER stress. XBP1 is known to induce the ER dexpansion and increase the expression of the ER chaperone genes to prtect the cell from the ER stress. We generated a mouse strain that lacked XBP1 specifically in the mouse intestine by breeding the XBP1flox mice with Villin-cre mice. Here we examined genes that are differentially expressed between WT and XBP1 KO mouse intestine to identify genes that are downstream of XBP1.
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.
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View SamplesIn order to study the gene expression profile in C57Bl/10 mouse blood, we exposed three different groups of animals. First was exposed to PO2 21% or normoxia. The second was exposed to chronic hypoxia (from PO2 21% to PO2 8%) and the third was also exposed to the same chronic hypoxia (CH) protocol but followed by two weeks under normoxia, and called as recovery group. The blood was extracted from inferior vena cava, the RNA was extracted, amplified and hybridized to Affimetrix MOE 430 V2.o chip. The results were analyzed using Partek Genome suite software. Using two fold cuttoff and 0% FDR parameters, we observed genes 512 diferentially expressed, of which one gene was up-regulated in both hypoxic and recovery condition, 202 were up-regulated during CH and then down-regulated after the recovery, 18 genes were down-regulated afteh CH and the up-regulated after recovery, ans finally 9 genes were down-regulated in both CH and recovery conditions.
Expression profiling reveals novel hypoxic biomarkers in peripheral blood of adult mice exposed to chronic hypoxia.
Age
View SamplesWe compared the aorta of 6-weeks-old mice (young) with 18-months-old mice (old). Using the publicly available tools Sylamer and DIANA-mirExTra, we identified an enrichment for miR-29 binding sites in the 3'UTR of genes downregulated in the aged aortas. We subsequently showed that inhibition of miR-29 in aged mice prevented dilation of the aorta.
MicroRNA-29 in aortic dilation: implications for aneurysm formation.
Age, Specimen part
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