H3K36me3 protects the mouse epigenome from single nucleotide variations

We adopt histone H3 mutants competitive incorporation system to screen the effects of them on genetic fidelity. We find incorporation of H3K36M, an oncogenic histone mutant, produce a cancer or ageing-like genetic landscape by punctuating the H3K36me3/H3K9me3 dependent DNA repair mechanism. This work firstly get a direct relationship between epigenetic inheritance and genomic stability In order to study the relationship between epigenetic dysregulation and genetic stability, we overexpress several histone H3 single-substitution mutants in mouse embryonic stem cells and get stable cell lines respectively carrying H3K36M or H3K9M. After a certain round culture, we analyze the genetic signature of these cells by high-throughput sequencing of exome-sequencing, ChIP-seq and aCGH. Comparing with the cells carrying wide-type H3 after identical culture condition, we summarize the genetic signature of histone mutation. Based on the surprising cross-talk between H3K36me3 and H3K9me3, we further find the mechanism of Suv39h modifier on the genetic stability.