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.
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.
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.
