Diagenode

Genetic variation at the 8q24.21 renal cancer susceptibility locus affects HIF binding to a MYC enhancer


Grampp S. et al.

Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel-Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have an impact on HIF pathways. A recent genome-wide association study on renal cancer susceptibility identified single-nucleotide polymorphisms (SNPs) in an intergenic region located between the oncogenes MYC and PVT1. Here using assays of chromatin conformation, allele-specific chromatin immunoprecipitation and genome editing, we show that HIF binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins. Moreover, we demonstrate that the risk-associated polymorphisms increase chromatin accessibility and activity as well as HIF binding to the enhancer. These findings provide further evidence that genetic variation at HIF-binding sites modulates the oncogenic transcriptional output of the VHL-HIF axis and provide a functional explanation for the disease-associated effects of SNPs in ccRCC.

Tags
Bioruptor
Antibody

Share this article

Published
October, 2016

Source

Products used in this publication

  • Antibody ChIP-seq grade icon
    C15410174
    H3K27ac polyclonal antibody

Events

  • Japanese Biochemical Society
    Yokohama
    Sep 18-Sep 20, 2019
  • The 2019 PacBio Long-Read Revolution: Highly Accurate and Affordable SMRT Sequencing
    Atlanta, Georgia
    Sep 19, 2019
  • The 2019 PacBio Long-Read Revolution: Highly Accurate and Affordable SMRT Sequencing
    RTP, North Carolina
    Sep 20, 2019
  • EpiGeneSys
    London
    Sep 22-Sep 24, 2019
 See all events

         Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics