Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA120359 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The Wnt/b-catenin signaling inhibits adipogenesis. Genome-wide profiling studies have revealed the enrichment of histone H3K27 methyltransferase PRC2 on Wnt genes. However, the functional significance of such a direct link between the two types of developmental regulators in mammalian cells, and the role of PRC2 in adipogenesis, remain unclear. Here we show PRC2 and its H3K27 methyltransferase activity are required for adipogenesis. PRC2 directly represses Wnt1, 6, 10a and 10b genes in preadipocytes and during adipogenesis. Deletion of the enzymatic Ezh2 subunit of PRC2 eliminates H3K27me3 on Wnt promoters and de-represses Wnt expression, which leads to activation of Wnt/b-catenin signaling and inhibition of adipogenesis. Ectopic expression of the wild type Ezh2, but not the enzymatically inactive F667I mutant, prevents the loss of H3K27me3 and the defects in adipogenesis in Ezh2-/- preadipocytes. The adipogenesis defects in Ezh2-/- cells can be rescued by expression of adipogenic transcription factors PPARa, C/EBPb, or inhibitors of Wnt/b-catenin signaling. Interestingly, Ezh2-/- cells show marked increase of H3K27 acetylation globally as well as on Wnt promoters. These results indicate that H3K27 methyltransferase PRC2 directly represses Wnt genes to facilitate adipogenesis, and suggest that acetylation and trimethylation on H3K27 play opposing roles in regulating Wnt expression. To identify additional PRC2-regulated genes in preadipocytes, we performed microarray analysis in Ezh2flox/flox preadipocytes infected with retroviruses expressing Cre or vector alone.
2010-03-19 | E-GEOD-20054 | biostudies-arrayexpress
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Project description:The Wnt/b-catenin signaling inhibits adipogenesis. Genome-wide profiling studies have revealed the enrichment of histone H3K27 methyltransferase PRC2 on Wnt genes. However, the functional significance of such a direct link between the two types of developmental regulators in mammalian cells, and the role of PRC2 in adipogenesis, remain unclear. Here we show PRC2 and its H3K27 methyltransferase activity are required for adipogenesis. PRC2 directly represses Wnt1, 6, 10a and 10b genes in preadipocytes and during adipogenesis. Deletion of the enzymatic Ezh2 subunit of PRC2 eliminates H3K27me3 on Wnt promoters and de-represses Wnt expression, which leads to activation of Wnt/b-catenin signaling and inhibition of adipogenesis. Ectopic expression of the wild type Ezh2, but not the enzymatically inactive F667I mutant, prevents the loss of H3K27me3 and the defects in adipogenesis in Ezh2-/- preadipocytes. The adipogenesis defects in Ezh2-/- cells can be rescued by expression of adipogenic transcription factors PPARa, C/EBPb, or inhibitors of Wnt/b-catenin signaling. Interestingly, Ezh2-/- cells show marked increase of H3K27 acetylation globally as well as on Wnt promoters. These results indicate that H3K27 methyltransferase PRC2 directly represses Wnt genes to facilitate adipogenesis, and suggest that acetylation and trimethylation on H3K27 play opposing roles in regulating Wnt expression.
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Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
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Project description:To investigate miRNAs that implicate the process of adipogenesis by interacting with canonical Wnt/β-catenin signaling pathway, we constructed two cell models at first, and then investigated the expression profile of microRNAs by using Microarray. Based on the data of high throughput microarray, we identified 18 miRNAs which might promote adipogenesis by repressing WNT signaling, including mir-210, mir-148a, mir-194, mir-322 etc. On the other hand, we also identified 29 miRNAs which might repress adipogenesis by activation of WNT signaling, including mir-344, mir-27, and mir-181. The target genes involved in WNT signaling pathway of these identified miRNAs were also predicted through online tools.
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Project description:To investigate miRNAs that implicate the process of adipogenesis by interacting with canonical Wnt/β-catenin signaling pathway, we constructed two cell models at first, and then investigated the expression profile of microRNAs by using Microarray. Based on the data of high throughput microarray, we identified 18 miRNAs which might promote adipogenesis by repressing WNT signaling, including mir-210, mir-148a, mir-194, mir-322 etc. On the other hand, we also identified 29 miRNAs which might repress adipogenesis by activation of WNT signaling, including mir-344, mir-27, and mir-181. The target genes involved in WNT signaling pathway of these identified miRNAs were also predicted through online tools. Two cell models of 3T3-L1, i.e. activation and suppression of WNT signaling including four samples, i.e. preadipocytes, mature adipocytes (MDI induction), Lithium treated preadipocytes, MDI induction of Lithium treated preadipocytes. Each sample was replicated in triplicate.
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