R-2-hydroxyglutarate-mediated inhibition of KDM4A disrupts telomere integrity

Isocitrate dehydrogenases 1 and 2 are mutated in more than 70% of low-grade glioma. This promotes the production of R-2-hydroxyglutarate (R-2HG) instead of α-ketoglutarate (αKG) and R-2HG will inhibit α-ketoglutarate enzymes like the lysine demethylase KDM4A. We hypothesized that KDM4A inhibition through R-2HG contribute to gliomagenesis. In our study, we showed that KDM4A inhibition leads to telomere defects. By ChIP-seq experiments, we demonstrated that KDM4A localized on telomeric repeats and that its depletion increased the level of H3K9me3 on telomeric chromatin. Chromatin immunoprecipitation DNA sequencing (ChIP-seq) for KDM4A in HeLa cells