Expression profile of deletion strain of yeast Mitochondrial Transcription factor 1 (mtf1∆)
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE55313 | GEO | 2015/12/30
SECONDARY ACCESSION(S): PRJNA239307
REPOSITORIES: GEO
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Project description:MTF1 is a highly conserved metal-binding transcription factor in eukaryotes. MTF1 binds to DNA sequence motifs, termed metal response elements (MREs) to induce the expression of genes involved in metal and oxidative stress homeostasis. MTF1 is responsive to both metal excess and deprivation, and can also protect cells from oxidative and hypoxic stresses. Disruption of metal homeostasis leads to the development of several pathological states. Despite its roles in these processes , MTF1 has been shown to be required for developmental processes such as embryonic liver formation. In this study, we used multiple strategies to understand the mechanism by which MTF1 functions in skeletal muscle differentiation and to determine the role cellular copper (Cu) status plays in this process. We provide the functional relationships between MTF1, Cu, myogenic gene promoters, and MyoD, an specific component of the myogenic transcriptional machinery in differentiating primary myoblasts derived from mouse satellite cells. We found that MTF1 is induced and translocated to the nucleus upon initiation of myogenesis. Consistent with previous studies from our laboratory , addition of non-toxic concentrations of Cu promote myogenesis and enhanced MTF1 expression. CRISPR/Cas9-mediated depletion of MTF1 demonstrated that MTF1 is essential for proper development of skeletal muscle, as partial Mtf1 knockdown leads to apoptosis to differentiating myoblasts. MTF1 was also found to bind Cu at a carboxy-terminal tetra-cysteine cluster, which may contribute to the mobilization of Cu to the nucleus during myogenesis. ChIP-seq and ChIP-qPCR analyses showed that MTF1 binds at the promoter regions of myogenic genes as part of a complex with MyoD, the master transcriptional regulator of the myogenic lineage. These results have the potential to initiate a new area of research in MTF1 function and in the regulation of myogenesis. Furthermore, these studies set the basis to understand the role of Cu at the transcriptional level, affects growth and development and will contribute to the largely unexplored are of muscular phenotypes observed in human pathologies associated to Cu misbalance, such as Menkes’ and Wilson’s diseases.
2019-10-04 | GSE116331 | GEO
Project description: Not available
| S-EPMC3074130 | biostudies-literature
Project description:Only a small number of genes are known direct targets of the zinc-responsive transcription factor MTF1; therefore, the aim of this study was to gain a more complete understanding of the MTF-1 regulated zinc-responsive component of the transcriptome. A targeted siRNA was used to deplete MTF1 expression in the human intestinal cell line Caco-2. We predicted that the response to zinc of direct MTF1 target genes would be abrogated by MTF1 knockdown. Surprisingly, a greater number of genes were regulated by zinc following MFT1 knockdown, and most genes that responded to zinc under both control and MTF1-depleted conditions had an augmented response in the latter condition. Exceptions were the zinc effluxer ZnT1 and a suite of metallothionein genes, suggesting that responses of other genes to zinc are usually buffered by increases in these proteins. We propose that MTF1 heads a hierarchy of zinc sensors, and through controlling the expression of a raft of metallothioneins and other key proteins involved in controlling intracellular zinc levels (e.g. ZnT1) alters zinc buffering capacity and total cellular zinc content. We tested and validated this model by overexpressing metallothionein and observing the predicted curtailment in response of the zinc-repressed SLC30A5 (ZnT5) promoter. The model provides the framework for an integrated understanding of cellular zinc homeostasis. Because MTs can bind metals other than zinc, this framework links with overall cellular metal homeostasis. Gene expression profiling by Illumina BeadArray of the effects of ZNF658 gene knockdown by siRNA. 2 different siRNAs were used, with appropriate non-targetting controls. All experiments were carried out in triplicate.
2016-02-24 | E-GEOD-76510 | biostudies-arrayexpress
Project description:Only a small number of genes are known direct targets of the zinc-responsive transcription factor MTF1; therefore, the aim of this study was to gain a more complete understanding of the MTF-1 regulated zinc-responsive component of the transcriptome. A targeted siRNA was used to deplete MTF1 expression in the human intestinal cell line Caco-2. We predicted that the response to zinc of direct MTF1 target genes would be abrogated by MTF1 knockdown. Surprisingly, a greater number of genes were regulated by zinc following MFT1 knockdown, and most genes that responded to zinc under both control and MTF1-depleted conditions had an augmented response in the latter condition. Exceptions were the zinc effluxer ZnT1 and a suite of metallothionein genes, suggesting that responses of other genes to zinc are usually buffered by increases in these proteins. We propose that MTF1 heads a hierarchy of zinc sensors, and through controlling the expression of a raft of metallothioneins and other key proteins involved in controlling intracellular zinc levels (e.g. ZnT1) alters zinc buffering capacity and total cellular zinc content. We tested and validated this model by overexpressing metallothionein and observing the predicted curtailment in response of the zinc-repressed SLC30A5 (ZnT5) promoter. The model provides the framework for an integrated understanding of cellular zinc homeostasis. Because MTs can bind metals other than zinc, this framework links with overall cellular metal homeostasis.
2016-02-24 | GSE76510 | GEO
Project description: Not available
| S-EPMC4558008 | biostudies-literature
Project description:Huntington’s disease (HD) is an inherited and incurable neurodegenerative disorder caused by CAG repeat expansions in the huntingtin (HTT) gene. The resulting mutant HTT protein alters cellular physiology at multiple levels, inducing toxicity and cell death. The mechanisms directly causing toxicity are partially understood, thus precluding the development of effective therapeutic strategies. Here we identified novel suppressors of mutant HTT toxicity by performing a genome-wide screen in pluripotent stem cells, followed by hit validation both in zebrafish and mouse HD models. The candidate suppressors identified were strongly enriched for HD-associated processes. We focused on Metal regulatory transcription factor 1 (Mtf1), a transcription factor controlling metal homeostasis in the cell. Forced expression of Mtf1 counteracts cell death, oxidative stress and transcriptional alterations caused by mutant HTT in pluripotent cells. In zebrafish, Mtf1 reduces malformations and apoptosis induced by mutant HTT, while Mtf1 delivery by Adeno-Associated viral (AAV) vectors ablated motor defects observed in an HD mouse model. Our data reveal that delivery of Mtf1 might act as a novel therapeutic strategy against HD and potentially other neurodegenerative disorders.
2023-05-30 | GSE166567 | GEO
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to use RNA-seq to find differences between WT and MTF1-KO tumor in colorectal cancer Methods: HCT116 cells and MTF1-KO HCT116 cells were injected subcutaneously into the back of NSG mice at 2x106 cells/recipient , At day 24 after injection，Tumor tissue were isolated from infected recipients，and Total RNA was collected. Besides,about 5x106 cultured HCT116 cells and MTF1-KO HCT116 cells were collected for total RNA isolation ,and sent all of them for sequencing. Conclusions: Our study represents the transcriptome difference between WT HCT116 tumor and MTF1-KO HCT116 tumor has a very positive significance for the pathological process of colorectal cancer，especially for cell adhension
2022-12-15 | GSE190435 | GEO
Project description:Verticillium transcription activator of adhesion 3 (Vta3) is required for plant root colonization and pathogenicity of the soil-borne vascular fungus Verticillium dahliae [Bui et al., 2018]. In this study, we discovered that Vta3 contributes to the virulence of V. dahliae on tomato plants by promoting ELV1 gene expression, which is not necessary for vegetative growth or production of conidiospores. Gene expression of the transcription factor Mtf1 is reduced in the presence of an intact VTA3 gene. The presence of an intact MTF1 gene triggers the expression of fungal effector genes and plant immune responses (transcription of tomato pathogenesis-related protein genes, and levels of pipecolic and salicylic acids functioning in tomato defense signaling against (hemi-) biotrophic pathogens), and is required for disease symptoms similar to those seen in tomato plants infected by the V. dahliae wild-type. Mtf1 promotes the formation of resting structures at the end of the infection cycle, which allows the fungus to survive in the soil and later to re-infect host plants. Protein pull-downs were performed with GFP-fused Vta3 to investigate whether there is evidence for a direct interaction of the regulators Vta3 and Mtf1. In this study, ribosomal proteins predominantly co-enriched with Vta3, and our data set did not give evidence that Mtf1 directly interacts with Vta3. Bui T-T, Harting R, Braus-Stromeyer SA, Tran V-T, Leonard M, Höfer A, et al. Verticillium dahliae transcription factors Som1 and Vta3 control microsclerotia formation and sequential steps of plant root penetration and colonisation to induce disease. New Phytologist. 2019;221: 2138–2159. doi:10.1111/nph.15514
2023-01-18 | PXD039123 | Pride
Project description: Not available
| S-EPMC7049685 | biostudies-literature
Project description:SF295 glioblastoma cells were subjected to CRISPR/Cas9-mediated knockout of the MTF1 (metal regulatory transcription factor 1) gene or non-targeted control (GFP). Two guides targeting MTF1 and one guide targeting GFP were cloned into the pXPR_023 all-in-one CRISPR/Cas9 vector. SF295 cells were transduced by lentiviral infection and selected using puromycin. Following selection, RNA was harvested from cell lines growing in culture. Wild-type SF295 cells were also included as a control. Anti-cancer uses of non-oncology drugs have been found on occasion, but such discoveries have been serendipitous and rare. To fully discover activity against multiple tumor types, resource-intensive screening across hundreds of cancer cell lines is needed. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. To accomplish this, we used PRISM, which involves the molecular barcoding of each cell line, followed by pooling of the barcoded lines. Relative barcode abundance following drug treatment versus controls thus reflects cell viability following drug treatment. We found that an unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines. Moreover, the killing activity of the majority of these drugs was predictable based on the molecular features of the cell lines. Mechanistic follow-up of several of these compounds revealed novel mechanisms. These results illustrate the potential of the PRISM drug repurposing resource as a starting point for new oncology therapeutic development.
2019-08-08 | GSE133285 | GEO