Diagenode

TET-Mediated Hypermethylation Primes SDH-Deficient Cells for HIF2α-Driven Mesenchymal Transition.


Morin A, Goncalves J, Moog S, Castro-Vega LJ, Job S, Buffet A, Fontenille MJ, Woszczyk J, Gimenez-Roqueplo AP, Letouzé E, Favier J

Loss-of-function mutations in the SDHB subunit of succinate dehydrogenase predispose patients to aggressive tumors characterized by pseudohypoxic and hypermethylator phenotypes. The mechanisms leading to DNA hypermethylation and its contribution to SDH-deficient cancers remain undemonstrated. We examine the genome-wide distribution of 5-methylcytosine and 5-hydroxymethylcytosine and their correlation with RNA expression in SDHB-deficient tumors and murine Sdhb cells. We report that DNA hypermethylation results from TET inhibition. Although it preferentially affects PRC2 targets and known developmental genes, PRC2 activity does not contribute to the DNA hypermethylator phenotype. We also prove, in vitro and in vivo, that TET silencing, although recapitulating the methylation profile of Sdhb cells, is not sufficient to drive their EMT-like phenotype, which requires additional HIF2α activation. Altogether, our findings reveal synergistic roles of TET repression and pseudohypoxia in the acquisition of metastatic traits, providing a rationale for targeting HIF2α and DNA methylation in SDH-associated malignancies.

Tags
MagMeDIP kit
Antibody
iDeal ChIP-qPCR

Share this article

Published
March, 2020

Source

Products used in this publication

  • ChIP-seq Grade
    C15410069
    H3K27me3 Antibody
  • ChIP kit icon
    C01010180
    iDeal ChIP-qPCR Kit
  • MagMeDIP qPCR Kit box
    C02010021
    MagMeDIP Kit

Events

 See all events

 


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