Project description:We report the high-throughput profiling of HIF1 in human kidney-2 cells (HK-2) under normoxia and 1% 24 hours hypoxia. By obtaining over two billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of HK-2 under normoxia and hypoxia. We found that HIF1 binds to both transcriptional starting sites and enhancer regions. This study provides novel insights into the epigenetic regulation of HIF1 in renal epithelial cells.
Project description:Hypoxia signature in Clear cell RCC A set of clear cell renal cell carcinomas were examined for the deregulation of hypoxia inducible and endocytosis regulated genes Tumor samples and Normal renal tissue GSE14762.rda contains an R data object
Project description:Hypoxia signature in Clear cell RCC A set of clear cell renal cell carcinomas were examined for the deregulation of hypoxia inducible and endocytosis regulated genes
Project description:Hypoxia is a hallmark of renal ischemia reperfusion injury (IRI) and serves as an essential regulator of innate immune responses during this process, although the mechanisms of this regulation remain unclear. Here, we show that dendritic cell (DC)-specific genetic ablation of hypoxia-inducible factor (HIF) 2α, a transcription factor induced by oxygen shortage, leads to hyperactivation of natural killer T cells (NKTs), ultimately exacerbating renal IRI in mice. HIF-2α deficiency in DCs triggers IFN-γ and IL-4 production in NKTs, along with upregulation of type I interferon (IFN) and chemokine responses critical for NKT activation. Mechanistically, loss of HIF-2α in DCs promotes their expression of CD36, a scavenger receptor for lipid uptake, resulting in increased lipid accumulation. Furthermore, HIF-2α binds directly to a reverse hypoxia-responsive element (rHRE) in the CD36 promoter, supporting its transcriptional regulation of CD36. Importantly, CD36 blockade by sulfo-N-succinimidyl oleate (SSO), reduces NKT activation and abolishes the exacerbation of renal IRI in mice with DC-specific HIF-2α knockout. Taken together, our study reveals a previously unrecognized role of a HIF-2α-CD36 regulatory axis in rewiring DC lipid metabolism under IRI-associated hypoxia, and suggests a potential therapeutic target to resolve long-standing obstacles in clinical treatment of this severe complication.
Project description:We report the application of chromatin immunoprecipitation and next generation sequencing technology for HIF1a binding sites at genome wide level in a RCC (renal cell carcinoma) cell line under hypoxia conditions. We found HIF1a binding sites in Caki-2 cell line under hypoxia conditions. Especially, we found HIF1a bind to SPOP under hypoxia condition, which was further validated. Examination of HIF1a binding sites in Caki-2 cell line under hypoxia condition
Project description:We report the application of chromatin immunoprecipitation and next generation sequencing technology for HIF1a binding sites at genome wide level in a RCC (renal cell carcinoma) cell line under hypoxia conditions. We found HIF1a binding sites in Caki-2 cell line under hypoxia conditions. Especially, we found HIF1a bind to SPOP under hypoxia condition, which was further validated.
Project description:We performed gene expression profiling of oligooxopiperazines (OPs) targeting the hypoxia-inducible transcription factor complex. Treatment of cells with OPs inhibited hypoxia-inducible gene expression in A549 cells.