EZH2 inhibition results in genome-wide PRC2 redistribution in cancer cell models

Upon EZH2 inhibitor treatment, PRC2 components EZH2 and SUZ12 are redistributed across the genome towards a small number of genomic loci that are refractory to H3K27me3 loss. Focal PRC2 accumulation and H3K27me3 retention occur primarily at CpG islands and transcription start sites of genes, with enrichment at canonical PRC2 nucleation sites. EZH2 and SUZ12 are present at low levels at actively transcribed TSSs, and this signal is lost with EZH2 inhibition. Overall design: ChIP-seq of PRC2 components, H3K27me3, and H3K4me3 upon treatment with EZH2 inhibitor or a control, in DLBCL and multiple myeloma cell lines.