Med23-dependent gene expression programs in T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE60779 | GEO | 2014/08/27
SECONDARY ACCESSION(S): PRJNA259533
REPOSITORIES: GEO
Similar Datasets
Project description:To analysis TCR induced Med23-dependent gene expression programs in T cells, we have employed microarray expression profiling as a discovery platform to identify genes with the potential to be regulated by Med23 in unstimulated or stimulated T cells. Mice CD4 T cells from wildtype and Med23 knockout mice were left unstimulated or stimulated for 6 hr, and gene expression difference was identified among four samples. Expression of seven genes (Med23, IFNg, IL2, Egr2, c-Fos, c-Jun and Foxp1) was validated in the same RNA samples by real-time PCR. TCR induced Med23-dependent gene expression was measured after unstimulation or stimulation for 6 hr in wildtype and Med23 knockout CD4 T cells.
2014-08-27 | E-GEOD-60779 | biostudies-arrayexpress
Project description:Affymetrix MOE430A arrays. Mouse embryonic fibroblasts (MEFs) from E11 passaged through crisis. Starved in 0.5% FBS for 16 h then stimulated by 20% serum final concentration for 30 minutes. The purpose was to identify genes affected by the loss of MED23 protein (subunit of the mediator complex). Samples were assayed in duplicate (Set 1 and Set 2) for starved state and serum state cells. Cells starved in low-serum (0.5%) for 16 h then add final conc. 20% FBS for 30 minutes. Harvest total RNA from duplicate samples. One sample set is kept starved and serves as the baseline. The other set is stimulated. This is done for both wild-type cell and the Med23-/- KO cells. We looked for gene expression fold changes greater than 2 (plus or minus) to find genes affected for serum stimulation by the loss of MED23, looking in detail at immediate early genes like Egr1.
2009-04-14 | E-GEOD-15638 | biostudies-arrayexpress
Project description:Affymetrix MOE430A arrays. Mouse embryonic fibroblasts (MEFs) from E11 passaged through crisis. Starved in 0.5% FBS for 16 h then stimulated by 20% serum final concentration for 30 minutes. The purpose was to identify genes affected by the loss of MED23 protein (subunit of the mediator complex). Samples were assayed in duplicate (Set 1 and Set 2) for starved state and serum state cells.
2009-04-14 | GSE15638 | GEO
Project description:Transcription profiling of unstimulated and stimulated mouse CD4+ T cells extracted from wild type (WT), hCD2-Egr2 transgenic (Egr2 Tg) and Egr2loxP/loxP hCD2-Cre Egr3-/- (Egr2/3 DKO) mice.
2015-05-17 | E-MTAB-2432 | biostudies-arrayexpress
Project description:K-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the “Ras-addiction” of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer. To gain a genome-wide understanding of how MED23 and ELK1 control gene expression in Ras-active lung cancer cells, we performed gene profiling experiments to analyze the transcriptomes from control, si-Med23, or si-Elk1 A549 cells.
2013-08-31 | GSE40517 | GEO
Project description:K-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the 'Ras-addiction' of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer. To gain a genome-wide understanding of how MED23 and ELK1 control gene expression in Ras-active lung cancer cells, we performed gene profiling experiments to analyze the transcriptomes from control, si-Med23, or si-Elk1 A549 cells. The si-Ctrl, si-Med23 and si-Elk1 A549 cells were cultured in the normal condition. Then the cells were harvested for RNA extraction and hybridization on Affymetrix microarrays. The analysis contain 9 samples. si-Ctrl cells have three replicates (si-Ctrl#1, si-Ctrl#2 and si-Ctrl#3), and the si-Med23 or si-Elk1 group contains three different cell lines that harbor three different RNAi oligos against Med23 or Elk1 (si-Med23A, B, C and si-Elk1A, B, C).
2013-08-31 | E-GEOD-40517 | biostudies-arrayexpress
Project description:In response to myeloablative stresses, HSCs are rapidly activated to replenish myeloid progenitors, while maintaining full potential of self-renewal to ensure life-long hematopoiesis. However, the key factors that orchestrate HSC activities during physiological stresses remain largely unknown. Here we report that Med23 controls the myeloid potential of activated HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Med23- deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are much easier to be activated in response to physio- logical stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is downregulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identify Med23 as a gatekeeper of myeloid potential of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid potential of HSCs and HSC activation upon stresses.
2018-07-14 | GSE112008 | GEO
Project description:To determine the role played by Med23 in OPC differentiation, OPCs were isolated from the Med23cKO (i.e., Med23-/-OPCs) or control mice (i.e., Med23+/+OPCs) and induced to differentiate in vitro. We then performed gene expression profiling analysis using data obtained from RNA-seq of Med23+/+iOLs and Med23-/-iOLs .
2024-10-23 | GSE226122 | GEO
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:Gene expression changes in stimulated and unstimulated Foxp1-deficient B cells.
| PRJNA337936 | ENA