Merm1/Wbscr22 is one of genes in chromosomal region deleted in Williams-Beuren syndrome, a multisystem developmental disorder. Wbscr22 contains a nuclear localization signal and an S-adenosyl-L-methionine-dependent methyltransferase fold, but its real function is completely unknown.In this study, to examine the function, we compared the gene expression profiles between control and Merm1/Wbscr22 knock-downed tumor cells.
The novel metastasis promoter Merm1/Wbscr22 enhances tumor cell survival in the vasculature by suppressing Zac1/p53-dependent apoptosis.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
Sex, Specimen part
View SamplesEmbryogenesis is tightly regulated by multiple levels of epigenetic systems such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent reprogramming occurs by de novo methylation and demethylation. Variance of DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analysed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions in the three germ layers and in the three adult somatic tissues are shared in common. This commonly methylated gene set is enriched in germ cell associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns with global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Taken together, our findings indicate that differentiation from ES cells to the three germ layers is accompanied by an increase in the number of commonly methylated DNA regions and that these tissue-specific alterations are present for only a small number of genes. Our findings indicate that DNA methylation at the proximal promoter regions of commonly methylated genes act as an irreversible mark which fixes somatic lineage by repressing transcription of germ cell specific genes.
DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
Sex, Specimen part
View SamplesEpigenetically silenced Ink4a-Arf locus is activated by loss of H3K27me3 in cellular senescence, where secreted factor expression is also involved. Here we analyzed epigenome and transcriptome alteration during Ras-induced senescence using mouse embryonic fibroblast (MEF). Seventeen genes with H3K27me3 loss and H3K4me3 gain showed marked upregulation, including p16Ink4a and Bmp2, a secreted factor for BMP/SMAD signal. Smad6, specific BMP/SMAD pathway inhibitor, was identified as the only one gene showing de novo H3K27 trimethylation with H3K4me3, resulting in strong repression. Ras-activated cells senesced with SMAD1/5/8 phosphorylation, and they escaped from senescence with decreased SMAD1/5/8 phosphorylation when introducing Smad6 or knocking-down Bmp2.
Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence.
Specimen part, Treatment
View SamplesBox C/D-type small nucleolar RNAs (snoRNAs) are functional RNAs responsible for mediating 2-O-ribose methylation of ribosomal RNAs (rRNAs) within the nucleolus. Previously, in relation to a novel chromosomal translocation in a human B-cell lymphoma, we identified U50HG, a non-protein-coding gene that hosted a box C/D-type U50 snoRNA within its intron. To investigate the physiological importance of the U50 snoRNA and its involvement in tumorigenesis, we generated a mouse model deficient in mouse U50 (mU50) snoRNA expression without altering the expression of mouse mU50 host-gene, mU50HG-b. The established mU50 snoRNA-deficient mice showed a significant reduction of mU50 snoRNA expression and the corresponding target rRNA methylation in various organs. Lifelong phenotypic monitoring showed that the mU50-deficient mice looked almost normal without accelerated tumorigenicity; however, a notable difference was the propensity for anomalies in the lymphoid organs.
Generation of a mouse model with down-regulated U50 snoRNA (SNORD50) expression and its organ-specific phenotypic modulation.
Specimen part
View SamplesRecent clinical data suggest that the efficacy of statin treatment in patients with heart failure varies depending on the drugs administered. Therefore, the present study was undertaken to compare murine cardiac gene expression following treatment with four different statins.
Comparative effects of statins on murine cardiac gene expression profiles in normal mice.
Sex, Specimen part
View SamplesTreatment of DBA/2J mice with a combination of L-methionine and valproic acid significantly attenuated progressive hearing loss. We examined gene expression in the whole cochlea of the mice. This study was aimed to detect genes of which change in expression levels were associated with attenuation of progressive hearing loss in the mice.
Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.
Sex, Age, Specimen part
View SamplesRetinal damage causes proliferation of Muller glia, but the degree of proliferation depends on mouse strains. Muller glial proliferation was significantly promoted by the addition of GSK3 inhibitor in 129, but not in B6. We used retinal explant culture as a model for retinal damage which caused preferential photoreceptor death in a few days.
Proliferation potential of Müller glia after retinal damage varies between mouse strains.
Age, Specimen part
View SamplesIncreasing the understanding of the impact of changes in oncogenes and tumor suppressor genes is essential for improving the management of lung cancer. Recently, we identified a new mouse lung-specific tumor suppressor - the G-protein coupled receptor 5A (Gprc5a). We sought to understand the molecular consequences of Gprc5a loss and towards this we performed microarray analysis of the transcriptomes of lung epithelial cells cultured from normal tracheas of Gprc5a knockout and wild-type mice to define a loss-of-Gprc5a gene signature. Moreover, we analyzed differential gene expression patterns between Gprc5a knockout normal lung epithelial cells as well as lung adenocarcinoma cells isolated and cultured from tumors of NNK-exposed Gprc5a knockout mice.
A Gprc5a tumor suppressor loss of expression signature is conserved, prevalent, and associated with survival in human lung adenocarcinomas.
Specimen part
View SamplesThe adult mammalian brain is composed of distinct regions that have specialized roles. The BF/POA regions are thought to have an important role in the regulation of sleep/wake behavior. However, genetic markers of the responsible cells for the regulation of sleep/wake behavior are largely unknown. To identify the molecular markers of the BF/POA regions, we sampled the BF/POA regions and compared gene expression in the BF/POA regions with those of other brain regions which we previously reported in the BrainStars (B*) project, in which we sampled ~50 small brain regions, including sensory centers and centers for motion, time, memory, fear, and feeding.
Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep.
Sex, Specimen part
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