Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA148383 | ENA |
REPOSITORIES: ENA
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Project description:Mediator Complex Regulates Alternative mRNA Processing via the Med23 Subunit
| PRJNA148321 | ENA
Project description:Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its Med23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit MED23 but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally Med23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that Med23 can regulate hnRNP L occupancy at their co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, suggesting a novel mechanism for coupling mRNA processing to transcription. Examination of hnRNP L and H3K36me3 enrichment in sictrl and si23 Hela cells
2012-02-24 | E-GEOD-33887 | biostudies-arrayexpress
Project description:Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its Med23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit MED23 but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally Med23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that Med23 can regulate hnRNP L occupancy at their co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, suggesting a novel mechanism for coupling mRNA processing to transcription. We performed an exon array experiment using HeLa cells expressing Med23, hnRNP L or control siRNAs which were established by a virus-mediated siRNA technology. Each sample was done in three biological replicates. Total RNA of these cell lines was processed and hybridized to the Affymetrix human exon array.
2012-02-24 | E-GEOD-33771 | biostudies-arrayexpress
Project description:Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its Med23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit MED23 but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally Med23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that Med23 can regulate hnRNP L occupancy at their co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, suggesting a novel mechanism for coupling mRNA processing to transcription.
2012-02-24 | GSE33771 | GEO
Project description:Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its Med23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit MED23 but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally Med23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that Med23 can regulate hnRNP L occupancy at their co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, suggesting a novel mechanism for coupling mRNA processing to transcription.
2012-02-24 | GSE33887 | GEO
Project description:Mediator complex function as an integrative hub for transcriptional regulation. Here we show that Mediator subunit MED23 regulate glucose and lipid metabolism via FOXO1 in liver. Here, we have generated a liver-specific Med23-knockout (LMKO) mouse and found that Med23-deletion in liver improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Mechanistically, MED23 participated in gluconeogenesis and cholesterol synthesis by interacting with FOXO1. Disruption of this interaction by hepatic Med23-deletion impaired the Mediator and RNAP II recruitment and partially reduced the expression of the FOXO1 target genes. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved insulin sensitivity. Overall, our data revealed Mediator MED23 as a critical regulator of glucose and lipid metabolism, suggesting novel therapeutic strategies against metabolic diseases.
2015-03-16 | GSE48966 | GEO
Project description:The Mediator complex functions as a control center orchestrating diverse signalings, gene activities, and biological processes. However, how Mediator subunits determine distinct cell fates remains to be fully elucidated. Here, we show that Mediator MED23 controls the cell fate preference that directs differentiation into smooth muscle cells (SMCs) or adipocytes. Med23-deficiency facilitates SMC differentiation but represses adipocyte differentiation from the multipotent mesenchymal stem cells. Gene profiling revealed that the presence or absence of Med23 oppositely regulates two sets of genes: the RhoA/MAL-targeted cytoskeleton/SMC genes and the Ras/ELK1 targeted growth/adipocyte genes. Mechanistically, MED23 favors ELK1-SRF binding to SMC gene promoters for repression, whereas the lack of MED23 favors MAL-SRF binding to SMC gene promoters for activation. Remarkably, the effect of MED23 on SMC differentiation can be recapitulated in zebrafish embryogenesis. Collectively, our data demonstrate the dual, opposing roles for MED23 in regulating the cytoskeleton/SMC and growth/adipocyte gene programs, suggesting its “Ying-Yang” function in directing adipogenesis vs. SMC differentiation. Examination of SRF enrichment in sictrl and si23 10T1/2 cells
2012-12-20 | E-GEOD-40369 | biostudies-arrayexpress
Project description:The Mediator subunit MED23 regulates inflammatory responses and liver fibrosis
| PRJNA565667 | ENA
Project description:Liver fibrosis, often associated with cirrhosis and hepatocellular carcinomas, is characterized by hepatic damage, an inflammatory response, and hepatic stellate cell (HSC) activation, although the underlying mechanisms are largely unknown.Here,we show that the MED23 subunit of the transcriptional Mediator complex participates in the development of experimental liver fibrosis. Compared with their control littermates, mice with hepatic Med23 deletion exhibited aggravated CCl4-induced liver fibrosis, with enhanced chemokine production and inflammatory infiltration as well as increased hepatocyte regeneration. Mechanistically, the orphan nuclear receptor RORα activates the expression of the liver fibrosis-related chemokines CCL5 and CXCL10, which is suppressed by the Mediator subunit MED23. We further found that the inhibition of Ccl5 and Cxcl10 expression by MED23 likely occurs due to G9a-mediated H3K9 dimethylation of the target promoters. Collectively, these findings reveal hepatic MED23 as a key modulator of chemokine production and inflammatory responses and define the MED23-CCL5/CXCL10 axis as a potential target for clinical intervention in liver fibrosis.
2020-06-06 | GSE137457 | GEO
Project description:Unraveling the mechanisms underlying early neural differentiation of ESCs is crucial to the cell-based therapies of neurodegenerate diseases. Neural fate acquisition is proposed to be controlled by a âdefaultâ mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of embryonic stem cells (ESCs). Unexpectedly we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23-depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of other Mediator subunit, Med1 or Med15, did not alter the neural differentiation of ESCs; and Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23-depletion attenuated the BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1 that is involved in the Bmp4 promoter-enhancer communication. Interestingly, Med23 knockdown in zebrafish embryos also enhanced the neural development at early embryogenesis, which could be reversible by coinjection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. We used microarrays to detail the global gene expression after MED23 knockout We examined the gene expression level in WT and MED23 knockout ES cells in steady culture condition.
2015-03-05 | E-GEOD-64500 | biostudies-arrayexpress