Open Chromatin and HIF-binding in renal tubular cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393644 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5814950.fastq.gz | Fastqsanger.gz | |||
| SRR5814951.fastq.gz | Fastqsanger.gz | |||
| SRR5814952.fastq.gz | Fastqsanger.gz | |||
| SRR5814943.fastq.gz | Fastqsanger.gz | |||
| SRR5814953.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 15 |
Similar Datasets
Project description:Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12.1. This defined a novel stage-specific mechanism in which the risk polymorphism, rs12814794, directly creates a new HIF-binding site that mediates HIF-1? isoform specific upregulation of its target BHLHE41. The alignment of multiple sites in the HIF cis-acting apparatus with RCC-susceptibility polymorphisms strongly supports a causal model in which minor variation in this pathway exerts significant effects on RCC development.
2017-07-11 | GSE101062 | GEO
Project description:Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12.1. This defined a novel stage-specific mechanism in which the risk polymorphism, rs12814794, directly creates a new HIF-binding site that mediates HIF-1? isoform specific upregulation of its target BHLHE41. The alignment of multiple sites in the HIF cis-acting apparatus with RCC-susceptibility polymorphisms strongly supports a causal model in which minor variation in this pathway exerts significant effects on RCC development.
2017-07-11 | GSE101063 | GEO
Project description:The activation of hypoxia-inducible transcription factors (HIF) leading to the expression of hundreds of target genes is a fundamental mechanism in acute and chronic kidney disease, mediating protective but possibly harmful effects. Furthermore, dysregulation of the HIF pathway in chronic kidney disease causes renal anemia through insufficient erythropoietin (EPO) induction in interstitial cells. RNA-seq analysis was performed in human primary renal tubular cells to analyse the effect of HIF stabilization on the expression of genes in tubular cells. ATAC-seq and HIF-CHIP-seq complement the data to analyse transcription factor binding and chromatin configuration changes.
2023-05-05 | GSE227848 | GEO
Project description:The activation of hypoxia-inducible transcription factors (HIF) leading to the expression of hundreds of target genes is a fundamental mechanism in acute and chronic kidney disease, mediating protective but possibly harmful effects. Furthermore, dysregulation of the HIF pathway in chronic kidney disease causes renal anemia through insufficient erythropoietin (EPO) induction in interstitial cells. RNA-seq analysis was performed in human primary renal tubular cells to analyse the effect of HIF stabilization on the expression of genes in tubular cells. ATAC-seq and HIF-CHIP-seq complement the data to analyse transcription factor binding and chromatin configuration changes.
2023-05-05 | GSE227823 | GEO
Project description:The activation of hypoxia-inducible transcription factors (HIF) leading to the expression of hundreds of target genes is a fundamental mechanism in acute and chronic kidney disease, mediating protective but possibly harmful effects. Furthermore, dysregulation of the HIF pathway in chronic kidney disease causes renal anemia through insufficient erythropoietin (EPO) induction in interstitial cells. RNA-seq analysis was performed in human primary renal tubular cells to analyse the effect of HIF stabilization on the expression of genes in tubular cells. ATAC-seq and HIF-CHIP-seq complement the data to analyse transcription factor binding and chromatin configuration changes.
2023-05-05 | GSE227821 | GEO
Project description:Clear cell renal cell carcinoma is characterized by loss of function of the von Hippel-Lindau tumor suppressor gene (VHL) and unrestrained activation of hypoxia inducible transcription factors (HIF). Genetic and epigenetic determinants can impact on HIF pathways. A recent genome-wide association study identified single nucleotide polymorphisms (SNPs) in an intergenic region on chromosome 8 that modify the risk of developing renal cancer. The SNPs are located in a putative regulatory region between the oncogenes MYC and PVT1. Using capture C assay and genome editing we show that HIF-binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins. Moreover, we demonstrate that the risk associated polymorphisms increase chromatin accessibility and activity as well as binding of HIF to the enhancer. These findings further strengthen the hypothesis that genetic variation at HIF-binding sites modulates the oncogenic transcriptional output of the VHL-HIF axis and provide a functional explanation for disease associated effects of SNPs in ccRCC.
2017-02-12 | GSE84444 | GEO
Project description:Activation of hypoxia-inducible transcription factors (HIF) leading to expression of hundred of target genes is a fundamental mechanism in acute and chronic kidney disease mediating protective but also possibly harmful effects. Furthermore, dysregulation of the HIF pathway in chronic kidney disease causes renal anemia through insufficient induction of erythropoietin (EPO) in interstitial cells. Hence, pharmacological compounds to treat renal anemia by stabilizing HIF have recently been introduced to the clinical practice. RNA-seq analysis was performed in primary renal tubular cells to analyse the effect of HIF stabilization on the expression of pathogenic Mucin1 (MUC1) variants. This study links the regulation of the kidney-disease gene MUC1 with the HIF-pathway in renal tubular cells.
2023-06-07 | GSE224177 | GEO
Project description:Multiomics analysis of HIF-stabilization in primary renal tubular cells
| PRJNA947174 | ENA
Project description:The course of Apolipoprotein 1 (APOL1) nephropathy is extremely heterogeneous and shaped by systemic factors such as the interferon response. However, additional environmental factors operating in a second-hit model have been less well defined. We identified an active regulatory DNA-element upstream of APOL1 that interacted with Hypoxia inducible factors (HIF). ATAC-seq, ChIP-seq and RNA-seq analysis were performed in podocytes to analyse the effect of HIF stabilization on the expression of pathogenic APOL1 variants. This study links the regulation of the kidney-disease gene APOL1 with the HIF-pathway in podocytes and renal tubular cells.
2023-04-26 | GSE224537 | GEO
Project description:The course of Apolipoprotein 1 (APOL1) nephropathy is extremely heterogeneous and shaped by systemic factors such as the interferon response. However, additional environmental factors operating in a second-hit model have been less well defined. We identified an active regulatory DNA-element upstream of APOL1 that interacted with Hypoxia inducible factors (HIF). ATAC-seq, ChIP-seq and RNA-seq analysis were performed in podocytes to analyse the effect of HIF stabilization on the expression of pathogenic APOL1 variants. This study links the regulation of the kidney-disease gene APOL1 with the HIF-pathway in podocytes and renal tubular cells.
2023-04-26 | GSE224536 | GEO