Similar Datasets
Project description:Pan-genomic analysis of hypoxic HIF-1a and HIF-2a binding by ChIP-seq in cancer cell lines
2022-11-15 | GSE200203 | GEO
Project description:ChIP-seq analysis of HIF-1b binding in hypoxic cancer cell lines
| PRJNA542174 | ENA
Project description:Hypoxia inducible factor (HIF) is the major transcriptional regulator of cellular responses to hypoxia. The two principal HIF-a isoforms, HIF-1a and HIF-2a, are progressively stabilized in response to hypoxia and form heterodimers with HIF-1b to activate a broad range of transcriptional responses. Here we report on the pan-genomic distribution of isoform-specific HIF binding in response to hypoxia of varying severity and duration, and in response to genetic ablation of each HIF-a isoform. Our findings reveal that, despite an identical consensus recognition sequence in DNA, each HIF heterodimer loads progressively at a distinct repertoire of cell-type specific sites across the genome, with little evidence of redistribution under any of the conditions examined. Marked biases towards promoter proximal binding of HIF-1 and promoter distant binding of HIF-2 were observed under all conditions and were consistent in multiple cell type. The findings imply that each HIF isoform has an inherent property that determines its binding distribution across the genome, which might be exploited to therapeutically target the specific transcriptional output of each isoform independently.
2018-10-06 | GSE120886 | GEO
Project description:Hypoxia inducible factor (HIF) is the major transcriptional regulator of cellular responses to hypoxia. The two principal HIF-a isoforms, HIF-1a and HIF-2a, are progressively stabilized in response to hypoxia and form heterodimers with HIF-1b to activate a broad range of transcriptional responses. Here we report on the pan-genomic distribution of isoform-specific HIF binding in response to hypoxia of varying severity and duration, and in response to genetic ablation of each HIF-a isoform. Our findings reveal that, despite an identical consensus recognition sequence in DNA, each HIF heterodimer loads progressively at a distinct repertoire of cell-type specific sites across the genome, with little evidence of redistribution under any of the conditions examined. Marked biases towards promoter proximal binding of HIF-1 and promoter distant binding of HIF-2 were observed under all conditions and were consistent in multiple cell type. The findings imply that each HIF isoform has an inherent property that determines its binding distribution across the genome, which might be exploited to therapeutically target the specific transcriptional output of each isoform independently.
2018-10-06 | GSE120885 | GEO
Project description:Macrophages (MФ) skewn towards a regulatory-like phenotype are known to promote tumor progression. They tend to accumulate in hypoxic tumor areas and activate hypoxia-inducible factors (HIF-1 and HIF-2). HIFs are known to alter the gene expression profile of MФ. To define direct HIF-1 and HIF-2 target genes in hypoxic and IL-10 treated human MФ we used chromatin immuno-precipitation-sequencing (ChIP-seq) and microarray analysis on a genome-wide scale.
2014-10-31 | GSE43109 | GEO
Project description:Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1 in the adaptive response, however, has not been determined. Here we investigate how HIF-1 influences hypoxic adaptation throughout Drosophila development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in dHIF mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIF and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIF in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs.
2013-02-05 | GSE33100 | GEO
Project description:Pan-genomic analysis of poly-adenylated transcript levels in normoxic and hypoxic cancer cell lines
2022-11-15 | GSE200204 | GEO
Project description:Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1 in the adaptive response, however, has not been determined. Here we investigate how HIF-1 influences hypoxic adaptation throughout Drosophila development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in dHIF mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIF and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIF in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs. Fly eggs were collected onto egg caps with yeast paste . The caps were replaced after overnight incubation periods and kept at 25M-BM-:C, until mid-L2. At mid-L2, larvae were transferred to a fresh egg cap with blue yeast paste (0.3% bromophenol blue), and allowed to develop until achieving the partial clear gut L3 stage (-10 to -4 hrs prior to metamorphic onset). Appropriately staged animals were moved to fresh agar plates and allowed to age an additional 6 hours at 25M-BM-:C (normoxic treatment). Alternatively, animals were placed in an airtight Modular Incubator Chamber for 6 hours at 25M-BM-:C after a gas mixture containing 4% oxygen balanced with nitrogen was flashed into the chamber (hypoxic treatment). Mutant larvae were sorted for the absence of GFP expression using dissecting stereoscope with fluorescence at mid-L2. Microarray analyses were performed on at least three biological replicates of w1118, dHIF mutants, or dERR mutants at the partial clear gut third instar larval stage and were treated for 6 hours in normoxia or 4% O2. For each biological replicate, at least 10 larvae were collected and washed with 1M-CM-^WPBS. Larvae were placed in TRIzol (Invitrogen, Carlsbad, CA) and homogenized using VWR disposable pellet mixer. Total RNA was isolated using a TRIzol/RQ1 DNase (Promega, Madison, WI) hybrid extraction protocol. Template labelings were performed using the GeneChip 3' IVT Express Kit according to the manufacturerM-bM-^@M-^Ys specifications (Affymetrix, Santa Clara, CA). Hybridizations to Affymetrix GeneChip Drosophila Genome 2.0 arrays were performed using the manufacturers recommendations. Every chip was scanned at a high resolution by the Affymetrix GeneChipM-BM-. Scanner 3000 according to the GeneChip Expression Analysis Technical Manual procedures (Affymetrix, Santa Clara, CA).
2013-02-05 | E-GEOD-33100 | biostudies-arrayexpress
Project description:The primary aim of this study was to evaluate the changes in hepatocyte gene expression under short-term hypoxic conditions in wild type and HIF-1a null cultures. To this end, hypoxia treated cultures were subjected to incubation with 1% O2/5% CO2/94% N2 at 37° C for eight hours prior to RNA isolation. Duplicate normoxic controls were established from separate animals wherein cultures were untreated and treated with Adbgal. Biological triplicates of wild type and HIF-1a null cultures were placed under hypoxic conditions and subsequently processed for microarray analysis. A total of 10 microarray hybridizations were performed. Keywords: repeat sample
2006-01-28 | GSE1321 | GEO
Project description:Mitochondria can be involved in regulating cellular stress response to hypoxia and tumor growth, but little is known about that mechanistic relationship. Here, we show that mitochondrial deficiency severely retards tumor xenograft growth with impairing hypoxic induction of HIF-1 transcriptional activity. Using mtDNA-deficient rho0 cells, we found that HIF-1 pathway activation was comparable in slow-growing rho0 xenografts and rapid-growing parental xenografts. Interestingly, we found that ex vivo rho0 cells derived from rho0 xenografts exhibited slightly increased HIF-1alpha expression and modest HIF-1 pathway activation regardless of oxygen concentration. Surprisingly, rho0 cells, as well as parental cells treated with oxidative phosphorylation inhibitors, were unable to boost HIF-1 transcriptional activity during hypoxia, although HIF-1alpha protein levels were ordinarily increased in these cells under hypoxic conditions. These findings indicate that mitochondrial deficiency causes loss of hypoxia-induced HIF-1 transcriptional activity and thereby might lead to a constitutive HIF-1 pathway activation as a cellular adaptation mechanism in tumor microenvironment.
2017-01-01 | GSE80320 | GEO