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

Open chromatin, HIF binding and mRNA expression analysis in podocytes (ChIP-Seq).

2023-04-26 | GSE224536 | GEO

Open chromatin, HIF binding and mRNA expression analysis in podocytes (ATAC-Seq).

2023-04-26 | GSE224535 | GEO

Open Chromatin and HIF-binding in renal tubular cells

Project description:Open Chromatin and HIF-binding in renal tubular cells

| PRJNA393644 | ENA

Open Chromatin and HIF-binding in renal tubular cells [FAIRE-seq]

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

Open Chromatin and HIF-binding in renal tubular cells [ChIP-seq]

2017-07-11 | GSE101063 | GEO

Open chromatin, HIF binding and mRNA expression analysis in podocytes

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-26 | GSE224538 | GEO