EZH2 gain-of-function mutations distort H3K27me3 landscapes and transform transcriptional responses to PRC2 inhibition [RNA-seq]

We have modelled several tumor-associated PRC2 mutations in a single isogenic system in order to reveal their comparative impacts on chromatin and transcription. We have also explored the link between EZH2 mutational status and abnormal H3K27 methylation in a unique longitudinal cohort of follicular lymphoma (FL) patient samples. Overall design: Differential analysis comparing gene expression profiles of WT vs PRC2 mutant immortalized mouse embryonic fibroblasts (iMEFs). The panel of PRC2 mutations encompasses: Ezh2-KO, Eed-KO, H3.3K27M, and the gain-of-function Y641F Ezh2 mutant (Ezh2Y641F). RNA-Seq was also used to profile gene expression changes in WT and Ezh2Y641F iMEFs treated with two doses of the EZH2 inhibitor UNC1999. Gene expression differential analysis between WT and EZH2 mutant FL samples, as measured by RNA-Seq.