GEO DataSets

(Submitter supplied) VHL loss is the most common genetic alteration event in ccRCC, but its effect on epigenetic landscape has not been elucidated previously. By performing histone modifications (H3K27ac, H3K4me1, H3K4me3) from ccRCC cell lines, we describe the genome-wide cis-regulatory landscapes of VHL-deficient ccRCC tumors. We show that ccRCCs exhibit a pervasive gain of enhancers around hypoxic and metabolic transcriptional targets.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

39 Samples

Download data: BED

(Submitter supplied) VHL loss is the most common genetic alteration event in ccRCC, but its effect on epigenetic landscape has not been elucidated previously. We describe the genome-wide cis-regulatory landscapes of VHL-deficient ccRCC tumors by comparing the epigenetic changes in terms of histone modifications (H3K27ac, H3K4me1, H3K4me3) with the transcriptomics profiles in 10 pairs of normal kidney and ccRCC tissues.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

20 Samples

Download data: BW

(Submitter supplied) VHL loss is the most common genetic alteration event in ccRCC. VHL loss stabilizes hypoxia-inducible factor-2 alpha (HIF2a). We compared the changes in transcriptomics profiles after VHL restoration or HIF2a siRNA knockdown in 786-O cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: BW

(Submitter supplied) VHL loss is the most common genetic alteration event in ccRCC. By profiling histone modifications from VHL-deficient ccRCC primary tumors and cell lines, we identifed tumor-associated promoters and enhancers. We next investigate whether VHL restoration alters tumor associated promoters and enhancers. We compared H3K27ac ChIP-seq with and without VHL restoration in 786-O cells. Restoration of wild-type VHL significantly altered a subset of tumor enhancers but affected promoters to a less extent.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

52 Samples

Download data: BED

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL11154 GPL16791

195 Samples

Download data: BED, BW

(Submitter supplied) VHL loss is the most common genetic alteration event in ccRCC. We profiled histone modifications from VHL-deficient ccRCC primary tumors and cell lines. We show that ccRCCs exhibit a pervasive gain of enhancers around hypoxic and metabolic transcriptional targets. Motif analysis using HOMER revealed significant enrichment of AP-1, ETS, NFĸB and HIFα in tumor enhancers. We generated ChIP-seq binding data for c-Jun, ETS1, NFĸB, and P300, a histone acetyltransferase, in 786-O cells. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

8 Samples

Download data: BED

(Submitter supplied) VHL loss is the most common genetic alteration event in ccRCC, but its effect on epigenetic landscape has not been elucidated previously. By performing histone modifications (H3K27ac, H3K4me1, H3K4me3) from ccRCC cell lines, we describe the genome-wide cis-regulatory landscapes of VHL-deficient ccRCC tumors. We show that ccRCCs exhibit a pervasive gain of enhancers around hypoxic and metabolic transcriptional targets.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

72 Samples

Download data: BED

(Submitter supplied) We are examining the regulatory pathway of ZHX2 and p65 in clear cell renal cell carcinoma cell line 786-O

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL17692 GPL16686

10 Samples

Download data: CEL, CHP

(Submitter supplied) Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bound VHL only when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target and its hydroxylation allowed VHL to regulate its protein stability. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

6 Samples

Download data: BW

(Submitter supplied) To unravel the potential cooperative roles of oxygen-regulated signaling pathways; von Hippel-Lindau (VHL) tumor suppressor protein and hypoxia-inducible factor (HIF) transcription factors, we have generated mutant mice with; Vhlh, Vhlh/Hif1α, Vhlh/Hif2α and Vhlh/Hif1α/Hif2α gene alleles floxed. Subsequently primary kidney cells were isolated, cultured and infected with Adenoviruses bearing either Cre/GFP or GFP expression only. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL10333

13 Samples

Download data: TXT

(Submitter supplied) Clear cell renal cell carcinoma (ccRCC) is characterized by a loss of tumor suppressor Von Hippel Lindau (VHL) function, which leads to accumulation of hypoxia inducible factor (including HIF1 and HIF2). HIF2 was previously reported to be one of the major oncogenic drivers in ccRCC, however its therapeutic targeting remains challenging. Here we performed a deubiquitinase (DUB) cDNA library binding screen and discovered that USP37 is a DUB that binds HIF2 and promotes HIF2 deubiquitination. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

17 Samples

Download data: TXT

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL20301

3 Samples

Download data: BW

(Submitter supplied) Clear cell renal cell carcinoma comprises two dominant subtypes, ccA and ccB, with gender disparity providing additional disease information. A third minor subgroup has distinct expression profiles consistent with von Hippel-Lindau wild type status and displays variant histology features.

Organism:

Homo sapiens

Type:

Expression profiling by array; Third-party reanalysis

Platform:

GPL4133

44 Samples

Download data: TXT

(Submitter supplied) The oncogenic potential of cancer-associated genetic alterations displays strong tissue-selectivity, the origins of which remain poorly understood. Here, we demonstrate that the lineage transcription factor PAX8 is essential for oncogenic signaling downstream of the most common genetic alterations causing clear cell renal cell carcinoma (ccRCC). Through interaction at a distal enhancer element PAX8 facilitates CCND1 expression by HIF2A, an oncogenic driver that is genetically activated due to VHL loss in ~90% of ccRCCs. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20301

38 Samples

Download data: BW

(Submitter supplied) The oncogenic potential of cancer-associated genetic alterations displays strong tissue-selectivity, the origins of which remain poorly understood. Here, we demonstrate that the lineage transcription factor PAX8 is essential for oncogenic signaling downstream of the most common genetic alterations causing clear cell renal cell carcinoma (ccRCC). Through interaction at a distal enhancer element PAX8 facilitates CCND1 expression by HIF2A, an oncogenic driver that is genetically activated due to VHL loss in ~90% of ccRCCs. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL20301 GPL24676

32 Samples

Download data: BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL20301 GPL24676

150 Samples

Download data: BW, TXT

(Submitter supplied) The oncogenic potential of cancer-associated genetic alterations displays strong tissue-selectivity, the origins of which remain poorly understood. Here, we demonstrate that the lineage transcription factor PAX8 is essential for oncogenic signaling downstream of the most common genetic alterations causing clear cell renal cell carcinoma (ccRCC). Through interaction at a distal enhancer element PAX8 facilitates CCND1 expression by HIF2A, an oncogenic driver that is genetically activated due to VHL loss in ~90% of ccRCCs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

48 Samples

Download data: TXT

(Submitter supplied) The oncogenic potential of cancer-associated genetic alterations displays strong tissue-selectivity, the origins of which remain poorly understood. Here, we demonstrate that the lineage transcription factor PAX8 is essential for oncogenic signaling downstream of the most common genetic alterations causing clear cell renal cell carcinoma (ccRCC). Through interaction at a distal enhancer element PAX8 facilitates CCND1 expression by HIF2A, an oncogenic driver that is genetically activated due to VHL loss in ~90% of ccRCCs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

32 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platform:

GPL20301

84 Samples

Download data: BED, BIGWIG, TXT

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

18 Samples

Download data: TXT