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| Status |
Public on Jul 11, 2017 |
| Title |
Open Chromatin and HIF-binding in renal tubular cells [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
This study consists of HIF ChIP-seq samples (HIF-1a and HIF-1b) from one individual and FAIRE-seq samples from three individuals
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| Contributor(s) |
Schödel J, Kranz F |
| Citation(s) |
28715484, 31690629 |
| |
| Submission date |
Jul 10, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Johannes Schödel |
| E-mail(s) |
Johannes.Schoedel@uk-erlangen.de
|
| Organization name |
FAU Erlangen-Nürnberg
|
| Street address |
Ulmenweg 18
|
| City |
Erlangen |
| ZIP/Postal code |
91054 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE101064 |
Open Chromatin and HIF-binding in renal tubular cells |
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| Relations |
| BioProject |
PRJNA393660 |
| SRA |
SRP111449 |
