Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Copper Regulation of HIF-1 Transcription Activity [ChIP-seq]

ABSTRACT: Copper (Cu) regulates hypoxia-inducible factor-1 (HIF-1) transcription activity by affecting the selectivity of HIF-1α targeting to the promoters of the affected genes. Here, we made an effort to provide a comprehensive understanding of Cu regulation of the selectivity of HIF-1α targeting across genome. We used tetraethylenepentamine (TEPA), a Cu selective chelator, to reduce Cu content in the cells. In hypoxia, we conducted chromatin immunoprecipitation combined with massively parallel DNA sequencing (ChIP-seq) to globally map the binding sites of HIF-1α, Pol Ⅱ (RNA polymeraseⅡ) and histone H3K27ac. We also performed RNA-sequencing (RNA-seq) in EA.hy926 cells under hypoxia (1% O2) with or without Cu depression to determine the profile of mRNA expression. Our analyses identified 3197 HIF-1α binding sites under hypoxia. Cu depression by TEPA reduced 1820 binding sites from the 3197, but induced additional 274 new binding sites. We analyzed these binding sites in the promoter and putative enhancer regions, coupled with their mRNA expression profiles, and found 281 Cu-dependent and 10 Cu-independent HIF-1α target genes. We found that the core bases “GGAA” and “TTCC” constituted the critical motifs for the binding sites of Cu-dependent genes. This study thus revealed that Cu, by affecting the binding of HIF-1α to the critical motifs in the promoter and putative enhancer regions of HIF-1 regulated genes, leads to the selectivity of HIF-1 regulated expression of Cu-dependent genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE120524 | GEO | 2019/09/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Copper Regulation of HIF-1 Transcription Activity [RNA-seq]

Project description:Copper (Cu) regulates hypoxia-inducible factor-1 (HIF-1) transcription activity by affecting the selectivity of HIF-1α targeting to the promoters of the affected genes. Here, we made an effort to provide a comprehensive understanding of Cu regulation of the selectivity of HIF-1α targeting across genome. We used tetraethylenepentamine (TEPA), a Cu selective chelator, to reduce Cu content in the cells. In hypoxia, we conducted chromatin immunoprecipitation combined with massively parallel DNA sequencing (ChIP-seq) to globally map the binding sites of HIF-1α, Pol Ⅱ (RNA polymeraseⅡ) and histone H3K27ac. We also performed RNA-sequencing (RNA-seq) in EA.hy926 cells under hypoxia (1% O2) with or without Cu depression to determine the profile of mRNA expression. Our analyses identified 3197 HIF-1α binding sites under hypoxia. Cu depression by TEPA reduced 1820 binding sites from the 3197, but induced additional 274 new binding sites. We analyzed these binding sites in the promoter and putative enhancer regions, coupled with their mRNA expression profiles, and found 281 Cu-dependent and 10 Cu-independent HIF-1α target genes. We found that the core bases “GGAA” and “TTCC” constituted the critical motifs for the binding sites of Cu-dependent genes. This study thus revealed that Cu, by affecting the binding of HIF-1α to the critical motifs in the promoter and putative enhancer regions of HIF-1 regulated genes, leads to the selectivity of HIF-1 regulated expression of Cu-dependent genes.

2019-09-24 | GSE120523 | GEO

Metronomic doxorubicin blocks HIF-1α-mediated responses in sarcomas and augments the effects of anti-VEGF-A therapy

Project description:Increased levels of hypoxia and hypoxia inducible factor 1α (HIF-1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged anti-angiogenic therapy of tumors can delay tumor growth but may also increase hypoxia and HIF-1α activity. In our recent clinical trial, treatment with the anti-vascular endothelial growth factor A (VEGF-A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene set enrichment analysis of microarrays from pre-treatment biopsies found the Gene Ontology category “Response to hypoxia” was upregulated in poor responders, and hierarchical clustering based on 140 hypoxia-responsive genes separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF-1α binding to DNA at low metronomic doses. We thus examined Dox treatment in 4 sarcoma cell lines, and found Dox at low concentrations (1-10 uM) blocked HIF-1α induction of VEGF-A by 84-97%, while inhibition of other HIF-1α-target genes including CA9, c-Met and FOXM1 was variable. HT1080 sarcoma xenografts had increased hypoxia and/or HIF-1α activity with increasing tumor size and with anti-VEGF receptor antibody (DC101) treatment. Combining DC101 and metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, primarily via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF-1α-target genes which may promote resistance to anti-angiogenic and other therapies. Metronomic Dox can block HIF-1α activation of target genes and works synergistically with anti-VEGF therapy to inhibit sarcomas. Pre-treatment biopsies were collected from 16 human sarcoma. The gene expression analysis was performed using Illumina platform.

2011-08-29 | E-GEOD-31715 | biostudies-arrayexpress

Genome-wide mapping of Hif-1α binding sites in zebrafish [ChIP-seq]

Project description:Analysis of the binding sites of Hif-1α in both wild-type and von Hippel Lindau mutant zebrafish lines at 4dpf by ChIP linked next generation sequencing. The von Hippel Lindau mutant displays a systemic hypoxic response under normoxic conditions. Results show the extent of Hif-1α binding to the genome, and provide a basis for analysis of the transcriptional response to genetically induced hypoxia in zebrafish.

2016-03-22 | GSE70727 | GEO

Transcription profiling of human U251 cells treated with hypoxia inducible factor HIF-1I siRNA or a polyamide targeted against the hypoxia response element (HRE) after induction of hypoxia

Project description:Transcription mediated by hypoxia inducible factor (HIF-1) contributes to tumor angiogenesis and metastasis but is also involved in the activation of cell-death pathways and normal physiological processes. Given the complexity of HIF-1 signaling it could be advantageous to target a subset of HIF-1 effectors rather than the entire pathway. We compared the genome-wide effects of three molecules that each interfere with the HIF-1-DNA interaction: a polyamide targeted to the hypoxia response element (HRE), siRNA targeted to HIF-1Î±, and echinomycin, a DNA binding natural product with a similar but less specific sequence preference to the polyamide. The polyamide affects a subset of hypoxia-induced genes that are consistent with the binding site preferences of the polyamide. For comparison, siRNA targeted to HIF-1α and echinomycin each affect the expression of nearly every gene induced by hypoxia. Remarkably, the total number of genes affected by either polyamide or HIF-1α siRNA over a range of thresholds is comparable. The data shows how polyamides can be used to affect a subset of a pathway regulated by a transcription factor. In addition, this study offers a unique comparison of three complementary approaches towards exogenous control of endogenous gene expression. Experiment Overall Design: Hypoxia-mimetic DFO (deferoxamine)-stimulated U251 cells that were treated with polyamide 1, HIF-1α siRNA, and echinomycin were compared to control cells that were also DFO-stimulated. Cells not stimulated with DFO were also compared to the DFO-stimulated controls. Three biological replicates were included for each treatment/condition.

2008-06-15 | E-GEOD-7835 | biostudies-arrayexpress

Effect of NDRG3 or HIF-1α knockdown on cell response to hypoxia

Project description:Analysis of Huh-7 hepatocarcinoma cell line depleted of NDRG3 or HIF-1α under hypoxic condition. HIF-1α and NDRG3 have distinct functions in hypoxia responses. Results provide insight into molecular basis of HIF-independent signaling in the development and progression of hypoxic tumors Gene expression profiles of Huh-7 cells stably expressing NDRG3-shRNA or HIF-1α-shRNA under normoxia were compared to gene expression profiles of Huh-7 stable cells under hypoxia for 6, 12 and 24 hours.

2015-07-24 | E-GEOD-55212 | biostudies-arrayexpress

Effect of NDRG3 expression on cell response to hypoxia

2015-07-24 | E-GEOD-59729 | biostudies-arrayexpress

Metronomic doxorubicin blocks HIF-1α-mediated responses in sarcomas and augments the effects of anti-VEGF-A therapy

2011-08-30 | GSE31715 | GEO

Integrated analysis of microRNA and mRNA expression and association with HIF binding in MCF-7 cells under hypoxia (miRNA-Seq)

Project description:Purpose: We aimed to investigate in depth the regulation of microRNA expression by hypoxia in the breast cancer cell line MCF-7, establish the relationship between microRNA expression and HIF binding sites, pri-miRNA transcription and microRNA processing gene expression. Methods: microRNA sequencing data and gene expression microarray data were generated from MCF-7 cells submitted to an hypoxia timecourse (16h, 32h and 48h at 1% Oxygen). Data was integrated to 500 published high-stringency HIF binding sites identified in MCF-7 cells. Results: We identified 41 microRNAs significantly up- and 28 down- regulated, of which 38 mature and 20 star forms are reported in conjunction with hypoxia for the first time. HIF-1α and HIF-2α binding sites within 50kb distance of microRNA loci were found by integration of HIF ChIP-seq data, showing overall association between binding sites and up-regulation. Gene expression profiling analysis showed no full coordination between pri-miRNA and microRNA expression, pointing towards additional levels of regulation. Several transcripts playing a role in microRNA processing were found regulated by hypoxia, of which two were HIF dependent. Conclusions: The data support the hypothesis that microRNA expression under hypoxia is regulated at transcriptional and post-transcriptional level. HIF is involved at both levels, regulating the transcription of certain microRNAs and also the expression of key elements of the microRNA processing pathway.

2014-02-13 | GSE47602 | GEO

Integrated analysis of microRNA and mRNA expression and association with HIF binding in MCF-7 cells under hypoxia [mRNA]

2014-02-13 | GSE47533 | GEO

Integrated analysis of microRNA and mRNA expression and association with HIF binding in MCF-7 cells under hypoxia [miRNA]

2014-02-13 | GSE47532 | GEO