{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE138nnn/GSE138342/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by genome tiling array"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138342"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Epigenetic pattern after EZH1,2 inhibition in lymohoma cells","description":"Although 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.","dates":{"publication":"2019/10/03"},"accession":"GSE138342","cross_references":{"GSM":["GSM4105747","GSM4105746","GSM4105745","GSM4105744","GSM4105743","GSM4105742","GSM4105741","GSM4105740","GSM4105749","GSM4105748","GSM4105736","GSM4105735","GSM4105734","GSM4105733","GSM4105732","GSM4105731","GSM4105730","GSM4105739","GSM4105738","GSM4105737","GSM4105725","GSM4105724","GSM4105723","GSM4105722","GSM4105721","GSM4105720","GSM4105729","GSM4105728","GSM4105727","GSM4105726","GSM4105794","GSM4105793","GSM4105792","GSM4105791","GSM4105790","GSM4105714","GSM4105713","GSM4105712","GSM4105799","GSM4105711","GSM4105798","GSM4105710","GSM4105797","GSM4105796","GSM4105795","GSM4105719","GSM4105718","GSM4105717","GSM4105716","GSM4105715","GSM4105783","GSM4105782","GSM4105781","GSM4105780","GSM4105789","GSM4105821","GSM4105788","GSM4105787","GSM4105820","GSM4105786","GSM4105785","GSM4105784","GSM4105709","GSM4105708","GSM4105707","GSM4105706","GSM4105705","GSM4105772","GSM4105771","GSM4105770","GSM4105813","GSM4105812","GSM4105779","GSM4105778","GSM4105811","GSM4105810","GSM4105777","GSM4105776","GSM4105775","GSM4105774","GSM4105773","GSM4105819","GSM4105818","GSM4105817","GSM4105816","GSM4105815","GSM4105814","GSM4105761","GSM4105760","GSM4105802","GSM4105769","GSM4105801","GSM4105768","GSM4105767","GSM4105800","GSM4105766","GSM4105765","GSM4105764","GSM4105763","GSM4105762","GSM4105809","GSM4105808","GSM4105807","GSM4105806","GSM4105805","GSM4105804","GSM4105803","GSM4105750","GSM4105758","GSM4105757","GSM4105756","GSM4105755","GSM4105754","GSM4105753","GSM4105752","GSM4105751","GSM4105759"],"GPL":["19784"],"GSE":["138342"],"taxon":["Homo sapiens"],"PMID":["[31747604]"]}}