Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence.

ABSTRACT: Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming. We characterize the reversibility of the alterations in DNA methylation, the histone landscape, and transcriptional reprogramming that occur following IDH1 mutation. We discover genome-wide coordinate changes in the localization and intensity of multiple histone marks and chromatin states. Mutant IDH1 establishes a CD24⁺ population with a proliferative advantage and stem-like transc

SUBMITTER: Turcan S 

PROVIDER: S-EPMC5769471 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature