Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-7835
PROVIDER: PRJNA100075 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This is a mathematical model comprised of non-linear ordinary differential equations describing the dynamic relationship between hypoxia-inducible factor-1 alpha (HIF-1a) mRNA, HIF-1a protein, and interleukin-15-mediated upstream signalling events in natural killer cells from human blood. Regulatory expressions are also included for mammalian target of rapamycin (mTOR), nuclear factor-kappa beta, and signal transducer and activator of transcription 3 (STAT3).
2024-09-02 | BIOMD0000000867 | BioModels
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that acts as a master regulator of oxygen homeostasis in metazoan species by binding to hypoxia response elements (HREs) and activating the transcription of hundreds of genes in response to reduced O2 availability. RNA polymerase II (Pol II) initiates transcription of many HIF target genes under non-hypoxic conditions, but pauses after 20-100 nucleotides and requires HIF-1 binding for release. Here we report that in hypoxic breast cancer cells, HIF-1 recruits TRIM28 and DNA-dependent protein kinase (DNA-PK) to HREs to release paused Pol II. We show that HIF-1α and TRIM28 assemble the catalytically-active DNA-PK heterotrimer, which phosphorylates TRIM28 at serine-824, enabling recruitment of CDK9, which phosphorylates serine-2 of the Pol II large subunit C-terminal domain and the negative elongation factor to release paused Pol II, thereby stimulating productive transcriptional elongation. Our studies have revealed a critical molecular mechanism by which HIF-1 stimulates gene transcription and suggest that the anticancer effects of drugs targeting DNA-PK in breast cancer may be due in part to their inhibition of HIF-dependent transcription.
2022-02-17 | PXD024373 | Pride
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression. Two-condition experiment, Normoxic MSCs vs. Hypoxic MSCs.
2011-02-19 | E-GEOD-20463 | biostudies-arrayexpress
Project description:Mesenchymal stromal cells (MSCs) are multipotent progenitors supporting bone marrow hematopoiesis. MSC have an efficient DNA damage response (DDR) and are consequently reatively radio-resistant cells. Therefore, MSCs are key to hematopoietic reconstitution following total body irradiation (TBI) and bone marrow transplantation (BMT). The bone marrow niche is hypoxic and via the heterodimeric transcription factor Hypoxia-inducible factor-1 (Hif-1), hypoxia enhances the DDR. Using gene knock-down, we have previously shown that the Hif-1α subunit of Hif is involved in MSC radio-resistance, however its exact mechanism of action remains unknown. In order to dissect the involvement of Hif-1α in the DDR, we have generated using CRISPR/Cas9 technology, a stable MS5 mouse MSC cell line lacking Hif-1 expression. Herein, we show that it is the whole Hif-1 transcription factor, and not only the Hif-1α subunit, that modulates the DDR of mouse MSCs, and that this effect is dependent upon the integrity of the DNA binding domain. We have also characterized the Hif-1α-dependent proteomic changes undergone by hypoxic MS5 cells. These findings have important implications for the modulation of MSC radio-resistance in the context of BMT and cancer.
2018-05-16 | PXD006701 | Pride
Project description:Hypoxia-inducible transcription factor HIF is the key regulator of hypoxia response. It is conserved from human to the model organism C. elegans. The homolog of HIF in C. elegans is HIF-1. In C. elegans, there are six alternative splicing isoforms for HIF-1. Isoform a (HIF1a) is the predominant one with important biological functions for stress response and longevity. Here, by performing chromatin immunoprecipitation DNA-sequencing (ChIP-seq), we identified the direct targets for HIF-1a at whole genome level.
2023-04-15 | GSE228846 | GEO
Project description:Hypoxia exacerbates tissue damage in inflammatory bowel disease (IBD). To counteract the deleterious effects of oxygen deprivation, cells within hypoxic tissues activate multiple adaptive mechanisms. Much attention has focused on adaptive pathways regulated by HIF (hypoxia inducible factor) transcription factors, and pharmacologic HIF stabilization is a promising therapeutic approach for IBD. However, recent evidence suggests that hypoxia-induction of cellular transcriptional programs can be mediated not only by HIF transcription factors, but also by oxygen-sensing epigenetic regulator, UTX. Here, we identify a key role for an UTX in modulating colitis severity. Unlike HIF-mediated pathways that act on gut epithelial cells, UTX-mediated pathways function in a T cell-intrinsic manner to protect against colitis. Hypoxia impairs the histone demethylase activity of UTX, which leads to accumulation of repressive H3K27me3 marks at IL12/STAT4 pathway genes (Il12rb2, Tbx21, and Ifng), decreased CD4+ T cell IFN-γ production, and increased CD4+ regulatory T cells (Tregs). Moreover, T cell specific UTX deletion protects mice from autoimmune colitis, which demonstrates that deactivation of UTX restores immune regulation in hypoxia-associated inflammation. Together these findings suggest that modulating UTX’s histone demethylase activity in T cells may be a new pharmacologic target for harnessing hypoxia-induced adaptive pathways in colitis.
2023-12-01 | GSE236299 | GEO
Project description:Hypoxia exacerbates tissue damage in inflammatory bowel disease (IBD). To counteract the deleterious effects of oxygen deprivation, cells within hypoxic tissues activate multiple adaptive mechanisms. Much attention has focused on adaptive pathways regulated by HIF (hypoxia inducible factor) transcription factors, and pharmacologic HIF stabilization is a promising therapeutic approach for IBD. However, recent evidence suggests that hypoxia-induction of cellular transcriptional programs can be mediated not only by HIF transcription factors, but also by oxygen-sensing epigenetic regulator, UTX. Here, we identify a key role for an UTX in modulating colitis severity. Unlike HIF-mediated pathways that act on gut epithelial cells, UTX-mediated pathways function in a T cell-intrinsic manner to protect against colitis. Hypoxia impairs the histone demethylase activity of UTX, which leads to accumulation of repressive H3K27me3 marks at IL12/STAT4 pathway genes (Il12rb2, Tbx21, and Ifng), decreased CD4+ T cell IFN-γ production, and increased CD4+ regulatory T cells (Tregs). Moreover, T cell specific UTX deletion protects mice from autoimmune colitis, which demonstrates that deactivation of UTX restores immune regulation in hypoxia-associated inflammation. Together these findings suggest that modulating UTX’s histone demethylase activity in T cells may be a new pharmacologic target for harnessing hypoxia-induced adaptive pathways in colitis.
2023-12-01 | GSE236300 | GEO
Project description:DNA methylation repels binding of hypoxia-inducible transcription factors to maintain tumour immunotolerance [SeqCapEpi]
| PRJNA338260 | ENA
Project description:<p>Natural killer (NK) cells are forced to cope with different oxygen environments even under resting conditions. The adaptation to low oxygen is regulated by oxygen-sensitive transcription factors, the hypoxia-inducible factors (HIFs). The function of HIFs for NK cell activation and metabolic rewiring remains controversial. Activated NK cells are predominantly glycolytic, but the metabolic programs that ensure the maintenance of resting NK cells are enigmatic. By combining <em>in situ</em> metabolomic and transcriptomic analyses in resting murine NK cells, our study defines HIF-1a as a regulator of tryptophan metabolism and cellular nicotinamide adenine dinucleotide (NAD+) levels. The HIF-1a/NAD+ axis prevents ROS production during oxidative phosphorylation (OxPhos) and thereby blocks DNA damage and NK cell apoptosis under steadystate conditions. In contrast, in activated NK cells under hypoxia, HIF-1a is required for glycolysis, and forced HIF-1a expression boosts glycolysis and NK cell performance <em>in vitro</em> and <em>in vivo</em>. Our data highlight two distinct pathways by which HIF-1a interferes with NK cell metabolism. While HIF-1a-driven glycolysis is essential for NK cell activation, resting NK cell homeostasis relies on HIF-1a-dependent tryptophan/NAD+ metabolism.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>RNA-seq data associated with this study are available in ArrayExpress (BioStudies): accession <a href='https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-12082' rel='noopener noreferrer' target='_blank'>E-MTAB-12082</a>.</p>
2023-06-01 | MTBLS6863 | MetaboLights