GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE138nnn/GSE138342/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by genome tiling arrayhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138342GEOGSEfalseEpigenetic pattern after EZH1,2 inhibition in lymohoma cellsAlthough global H3K27me3 reprogramming is a hallmark of cancer, no effective therapeutic strategy for H3K27me3-high malignancies harboring EZH2WT/WT has yet been established. We explored epigenome and transcriptome in EZH2WT/WT aggressive lymphomas, and found that mutual interference and compensatory function of co-expressed EZH1 and EZH2 rearrange their own genome-wide distribution, thereby establishing restricted chromatin and gene expression signatures. Direct comparison of leading compounds introduced potency and a mechanism-of-action of the EZH1/2 dual-inhibitor (valemetostat). The synthetic lethality was observed in all lymphoma models and primary adult T-cell leukemia–lymphoma (ATL) cells. Opposing actions of EZH1/2-polycomb and SWI/SNF complexes are required for facultative heterochromatin formation. Inactivation of chromatin-associated genes (ARID1A, SMARCA4/BRG1, SMARCB1/SNF5, KDM6A/UTX, BAP1, KMT2D/MLL2) and oncovirus infection (HTLV-1, EBV) trigger EZH1/2 perturbation and H3K27me3 deposition. Our study provides the mechanism-based rationale for chemical dual-targeting of EZH1/2 in cancer epigenome.2019/10/03GSE138342GSM4105747GSM4105746GSM4105745GSM4105744GSM4105743GSM4105742GSM4105741GSM4105740GSM4105749GSM4105748GSM4105736GSM4105735GSM4105734GSM4105733GSM4105732GSM4105731GSM4105730GSM4105739GSM4105738GSM4105737GSM4105725GSM4105724GSM4105723GSM4105722GSM4105721GSM4105720GSM4105729GSM4105728GSM4105727GSM4105726GSM4105794GSM4105793GSM4105792GSM4105791GSM4105790GSM4105714GSM4105713GSM4105712GSM4105799GSM4105711GSM4105798GSM4105710GSM4105797GSM4105796GSM4105795GSM4105719GSM4105718GSM4105717GSM4105716GSM4105715GSM4105783GSM4105782GSM4105781GSM4105780GSM4105789GSM4105821GSM4105788GSM4105787GSM4105820GSM4105786GSM4105785GSM4105784GSM4105709GSM4105708GSM4105707GSM4105706GSM4105705GSM4105772GSM4105771GSM4105770GSM4105813GSM4105812GSM4105779GSM4105778GSM4105811GSM4105810GSM4105777GSM4105776GSM4105775GSM4105774GSM4105773GSM4105819GSM4105818GSM4105817GSM4105816GSM4105815GSM4105814GSM4105761GSM4105760GSM4105802GSM4105769GSM4105801GSM4105768GSM4105767GSM4105800GSM4105766GSM4105765GSM4105764GSM4105763GSM4105762GSM4105809GSM4105808GSM4105807GSM4105806GSM4105805GSM4105804GSM4105803GSM4105750GSM4105758GSM4105757GSM4105756GSM4105755GSM4105754GSM4105753GSM4105752GSM4105751GSM410575919784138342Homo sapiens[31747604]