Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD002073
PROVIDER: PRJNA278389 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1910470.fastq.gz | Fastqsanger.gz | |||
| SRR1916550.fastq.gz | Fastqsanger.gz | |||
| SRR1910471.fastq.gz | Fastqsanger.gz | |||
| SRR1916551.fastq.gz | Fastqsanger.gz | |||
| SRR1916542.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:MYC is an oncoprotein transcription factor that is overexpressed in the majority cancers. Although MYC itself is considered undruggable, it may be possible to inhibit MYC by targeting the co-factors it uses to drive oncogenic gene expression patterns. Here, we use loss- and gain- of function approaches to interrogate how one MYC co-factor—Host Cell Factor (HCF)-1—contributes to MYC activity in a Burkitt lymphoma setting. We identify high-confidence direct targets of the MYC–HCF-1 interaction that are regulated through a recruitment-independent mechanism, including genes that control mitochondrial function and rate-limiting steps for ribosome biogenesis and translation. We describe how these gene expression events impact cell growth and metabolism, and demonstrate that the MYC–HCF-1 interaction is essential for tumor maintenance in vivo. This work highlights the MYC–HCF-1 interaction as a focal point for development of novel anti-cancer therapies.
2020-07-15 | ST001429 | MetabolomicsWorkbench
Project description:MYC enhances protein synthesis by regulating genes involved in ribosome biogenesis and protein translation. Here, we show that MYC-induced protein translation is mediated by the transcription factor aryl hydrocarbon receptor (AHR), which is induced by MYC in colonic cells. AHR promotes protein synthesis by activating the transcription of genes required for ribosome biogenesis and protein translation, including OGFOD1 and NOLC1. Using surface sensing of translation (SUnSET) to measure global protein translation, we found that silencing AHR or its targets diminishes protein synthesis. Therefore, targeting AHR or its downstream pathways could provide a novel approach to limit biomass production in MYC-driven tumors.
2019-07-30 | GSE135061 | GEO
Project description:b'MYC is an oncoprotein transcription factor that is overexpressed in the majority cancers. Although MYC itself is considered undruggable, it may be possible to inhibit MYC by targeting the co-factors it uses to drive oncogenic gene expression patterns. Here, we use loss- and gain- of function approaches to interrogate how one MYC co-factorHost Cell Factor (HCF)-1contributes to MYC activity in a Burkitt lymphoma setting. We identify high-confidence direct targets of the MYCHCF-1 interaction that are regulated through a recruitment-independent mechanism, including genes that control mitochondrial function and rate-limiting steps for ribosome biogenesis and translation. We describe how these gene expression events impact cell growth and metabolism, and demonstrate that the MYCHCF-1 interaction is essential for tumor maintenance in vivo. This work highlights the MYCHCF-1 interaction as a focal point for development of novel anti-cancer therapies.'
2021-02-17 | MSV000086896 | GNPS
Project description:Regulatory T (Treg) cell activation and expansion during neonatal life and in response to inflammation are critical for immunosuppression, yet the mechanisms governing these events are incompletely understood. We report that the oncogene and transcriptional regulator c-Myc (Myc) controls immune homeostasis through regulation of Treg cell accumulation and functional activation. Myc activity is enriched in Treg cells generated during neonatal life and responding to inflammation. Myc-deficient Treg cells show cell-intrinsic defects in overall accumulation and ability to transition to an activated state during early life or acute inflammation. Consequently, loss of Myc in Treg cells results in a rapid, early-onset autoimmune disorder accompanied by uncontrolled effector CD4+ and CD8+ T cell responses. We also provide evidence that Myc regulates mitochondrial oxidative metabolism but is dispensable for fatty acid oxidation (FAO). Indeed, Treg cell-specific deletion of Cox10, which is required for oxidative phosphorylation, but not Cpt1a, the rate-limiting enzyme for FAO, results in impaired Treg cell function and maturation. Thus, Myc coordinates Treg cell accumulation, transitional activation and metabolic programming to orchestrate immune homeostasis. We used microarrays to compare the global transcription profiles of WT and Myc-null Treg cells.
2020-01-10 | GSE141499 | GEO
Project description:Embryonic genome activation (EGA) is orchestrated by an intrinsic developmental program initiated during oocyte maturation with translation of stored maternal mRNAs. Here we show that tankyrase, a poly(ADP-ribosyl) polymerase that regulates β-catenin levels, undergoes programmed translation during oocyte maturation and serves an essential role in mouse EGA. Newly translated TNKS triggers proteasomal degradation of axin, reducing targeted destruction of β-catenin and promoting β-catenin-mediated transcription of target genes, including Myc. MYC mediates ribosomal RNA transcription in 2-cell embryos, supporting global protein synthesis. Suppression of tankyrase activity using knockdown or chemical inhibition causes loss of nuclear β-catenin and global reductions in transcription and histone H3 acetylation. Chromatin and transcriptional profiling indicate that development arrests prior to the mid-2-cell stage, mediated in part by reductions in β-catenin and MYC. These findings indicate that post-transcriptional regulation of tankyrase serves as a ligand-independent developmental mechanism for post-translational β-catenin activation and is required to complete EGA.
2020-05-21 | GSE123815 | GEO
Project description:Dysregulation of the proto-oncogene c-Myc (MYC henceforward) drives malignant progression, but also induces robust anabolic and proliferative programs leading to intrinsic stress. The mechanisms enabling adaptation to MYC-induced stress are not fully understood. We have uncovered an essential role for the transcription factor ATF4 in cell survival following MYC activation. MYC- upregulates ATF4 by activating GCN2 kinase through uncharged tRNAs. Subsequently, ATF4 co-occupies promoter regions of over 30 MYC target genes, including those regulating amino acid biosynthesis/transport and protein synthesis. ATF4 is essential for MYC-induced upregulation of the negative translational regulator and mTOR target 4E-BP1 and genetic or pharmacological inhibition of mTOR signaling rescues ATF4 deficient cells from MYC-induced stress. Acute deletion of ATF4 significantly delays MYC-driven tumor progression and increases survival in mouse models. Our results establish ATF4 as a cellular rheostat of MYC-activity, ensuring enhanced translation rates are compatible with survival and tumor progression.
2018-07-18 | GSE117240 | GEO
Project description:Mucosal associated invariant T (MAIT) cells are an abundant population of innate T cells that recognize bacterial ligands and play a key role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells undergo proliferative expansion and increase their production of effector molecules such as cytokines. In this study, we found that mRNA and protein the abundance of the key metabolism regulator and transcription factor MYC was increased in stimulated MAIT cells. Using quantitative mass spectrometry, we identified the activation of two MYC controlled metabolic pathways, amino acid transport and glycolysis, both of which were necessary for MAIT cell proliferation. Finally, we showed that MAIT cells isolated from people with obesity showed decreased MYC mRNA abundance upon activation, which was associated with defective MAIT cell proliferation and functional responses. Collectively, our data uncovers the importance of MYC-regulated metabolism for MAIT cell proliferation and provides additional insight into the molecular basis for the functional defects of MAIT cells in obesity.
2023-04-20 | PXD041544 | Pride
Project description:We descrive a joint model of transcriptional activation and mRNA accumulation, using estrogen receptor ERM-NM-1 activation in MCF-7 breast cancer cell line, which can be used for inference of transcription rate, RNA processing delay and degradation rate given data from high-throughput sequencing time course experiments. MCF-7 cells were mock treated or with 10nM 17b-E2 to nine time points (5', 10', 20', 40', 80', 160', 320', 640' and 1280'). Genome-wide identification of RNA polymerase II (RNAPII) occupancy and transcriptome profiling (RNA-seq) following E2 induction of MCF-7 cells Please note that the information in the wig.txt files is in gene-specific coordinates, not chromosomic coordinates, as this is the most sensible format for the associated project/paper.
2015-03-04 | E-GEOD-62789 | biostudies-arrayexpress
Project description:The 12-hour clock coordinates lipid homeostasis, energy metabolism and stress rhythms via the transcriptional regulator XBP1. However, the biochemical and physiological basis for integrated control of the 12-hour clock and diverse metabolic pathways remains unclear. Here, we show that steroid receptor coactivator SRC-3 coactivates XBP1 transcription and regulates hepatic 12-hour cistrome and gene rhythmicity. Mice lacking SRC-3 show abnormal 12-hour rhythms in hepatic transcription, metabolic functions, systemic energetics, and rate-limiting lipid metabolic processes including triglyceride, phospholipid and cardiolipin pathways. Notably, 12-hour clock coactivation is not only preserved, with its cistromic activation priming ahead of the zeitgeber cue of light, but concomitant with rhythmic remodeling in the absence of food. These findings reveal that SRC-3 integrates the mammalian 12-hour clock, energy metabolism, and membrane and lipid homeostasis, and demonstrates a role for the 12-hour clock machinery as an active transcriptional mechanism in anticipating physiological and metabolic energy needs and stresses.
2022-02-04 | ST002079 | MetabolomicsWorkbench
Project description:The mammalian neocortex comprises an enormous diversity regarding cell types, morphology, and connectivity. In this work, we discover a post-transcriptional mechanism of gene expression regulation, protein translation, as a determinant of cortical neuron identity. We find specific upregulation of protein synthesis in the progenitors of later-born neurons and show that translation rates and concomitantly protein half-lives are inherent features of cortical neuron subtypes. In a small molecule screening, we identify Ire1a as a regulator of Satb2 expression and neuronal polarity. In the developing brain, Ire1a regulates global translation rates, coordinates ribosome traffic, and the expression of eIF4A1. Furthermore, we demonstrate that the Satb2 mRNA translation requires eIF4A1 helicase activity towards its 5’-untranslated region. Altogether, we show that cortical neuron diversity is generated by mechanisms operating beyond gene transcription, with Ire1a-safeguarded proteostasis serving as an essential regulator of brain development.
2024-01-10 | GSE172489 | GEO