Figure 1

The IDH1 mutation leads to gene down-regulation, DNA methylation and histone hypo-acetyalation: three E12 murine neurosphere lines were created and infected with an IDH1 mutant over-expression vector (“E12 neurospheres”)³⁷. Additionally cell lines were created from ex-planted mouse tumors from a previously published IDH1 mutant mouse glioma model (“Nunez et al.³⁸”). (A) IDH1 wildtype and IDH1 mutant lines were compared using RNA-seq analysis revealing that IDH1 mutant samples are associated with gene down-regulation. (B) IDH1 wildtype and IDH1 mutant (N = 3 lines) murine E12 neurosphere lines underwent reduced bisulfite sequencing and the numbers of methylated islands were tallied confirming previous findings that IDH1 mutant samples are associated with hyper-methylation. (C) E12 neurospheres (N = 3) and the Nunez et al. glioma model (N = 1) underwent ATAC-seq analysis and revealed a non-significant trend for IDH1 mutant samples to have more peaks. (D,E) E12 neurospheres (N = 3) and Nunez et al. glioma cell lines (N = 3) underwent ChIP-seq with antibodies against H3K27me3 (D) and H3K27ac (E) revealing that the IDH1 mutation is associated with H3K27 hypoacetylation and a more modest trend towards H3K27 hypomethylation.