Accession	GSE138342
Status	2019/10/3
Title	Epigenetic pattern after EZH1,2 inhibition in lymohoma cells
Organism	Homo sapiens
Experiment type	Genome binding/occupancy profiling by genome tiling array
Summary	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.
Samples	GSM ID Sample info Characteristics Description GSM4105707 Normal2_2_controlIgG cell type:Normal CD4+ T-cell - GSM4105708 Normal2_2_EZH2 cell type:Normal CD4+ T-cell - GSM4105708 Normal2_2_EZH2 cell type:Normal CD4+ T-cell - GSM4105709 Normal2_controlIgG cell type:Normal CD4+ T-cell - GSM4105709 Normal2_controlIgG cell type:Normal CD4+ T-cell - GSM4105710 Normal2_EZH1 cell type:Normal CD4+ T-cell - GSM4105727 TL-Om1_OR-S2_EZH1 cell type:ATL cell line - GSM4105728 TL-Om1_DMSO_EZH2 cell type:ATL cell line - GSM4105710 Normal2_EZH1 cell type:Normal CD4+ T-cell - GSM4105728 TL-Om1_DMSO_EZH2 cell type:ATL cell line - GSM4105711 Normal2_EZH2 cell type:Normal CD4+ T-cell - GSM4105729 TL-Om1_GSK126_EZH2 cell type:ATL cell line - GSM4105729 TL-Om1_GSK126_EZH2 cell type:ATL cell line - GSM4105730 TL-Om1_OR-S1_EZH2 cell type:ATL cell line - GSM4105730 TL-Om1_OR-S1_EZH2 cell type:ATL cell line - GSM4105731 TL-Om1_OR-S2_EZH2 cell type:ATL cell line - GSM4105711 Normal2_EZH2 cell type:Normal CD4+ T-cell - GSM4105731 TL-Om1_OR-S2_EZH2 cell type:ATL cell line - GSM4105732 TL-Om1_DMSO_YY1 cell type:ATL cell line - GSM4105712 Normal3_controlIgG cell type:Normal CD4+ T-cell - GSM4105732 TL-Om1_DMSO_YY1 cell type:ATL cell line - GSM4105712 Normal3_controlIgG cell type:Normal CD4+ T-cell - GSM4105733 TL-Om1_GSK126_YY1 cell type:ATL cell line - GSM4105713 Normal3_EZH1 cell type:Normal CD4+ T-cell - GSM4105733 TL-Om1_GSK126_YY1 cell type:ATL cell line - GSM4105713 Normal3_EZH1 cell type:Normal CD4+ T-cell - GSM4105734 TL-Om1_OR-S1_YY1 cell type:ATL cell line - GSM4105734 TL-Om1_OR-S1_YY1 cell type:ATL cell line - GSM4105735 TL-Om1_OR-S2_YY1 cell type:ATL cell line - GSM4105735 TL-Om1_OR-S2_YY1 cell type:ATL cell line - GSM4105736 TL-Om1_DMSO_H3K4me3 cell type:ATL cell line - GSM4105714 Normal3_EZH2 cell type:Normal CD4+ T-cell - GSM4105736 TL-Om1_DMSO_H3K4me3 cell type:ATL cell line - GSM4105714 Normal3_EZH2 cell type:Normal CD4+ T-cell - GSM4105737 TL-Om1_GSK126_H3K4me3 cell type:ATL cell line - GSM4105715 ATL1_controlIgG cell type:ATL patient PBMC - GSM4105737 TL-Om1_GSK126_H3K4me3 cell type:ATL cell line - GSM4105715 ATL1_controlIgG cell type:ATL patient PBMC - GSM4105738 TL-Om1_OR-S1_H3K4me3 cell type:ATL cell line - GSM4105716 ATL1_EZH1 cell type:ATL patient PBMC - GSM4105738 TL-Om1_OR-S1_H3K4me3 cell type:ATL cell line - GSM4105716 ATL1_EZH1 cell type:ATL patient PBMC - GSM4105739 TL-Om1_OR-S2_H3K4me3 cell type:ATL cell line - GSM4105717 ATL1_EZH2 cell type:ATL patient PBMC - GSM4105739 TL-Om1_OR-S2_H3K4me3 cell type:ATL cell line - GSM4105781 TL-Om1_shEZH1_H3K27me3 cell type:ATL cell line - GSM4105782 TL-Om1_shEZH2_H3K27me3 cell type:ATL cell line - GSM4105717 ATL1_EZH2 cell type:ATL patient PBMC - GSM4105740 TL-Om1_shCtrl_EZH1 cell type:ATL cell line - GSM4105740 TL-Om1_shCtrl_EZH1 cell type:ATL cell line - GSM4105741 TL-Om1_shEZH1_1_EZH1 cell type:ATL cell line - GSM4105741 TL-Om1_shEZH1_1_EZH1 cell type:ATL cell line - GSM4105718 ATL2_controlIgG cell type:ATL patient PBMC - GSM4105718 ATL2_controlIgG cell type:ATL patient PBMC - GSM4105782 TL-Om1_shEZH2_H3K27me3 cell type:ATL cell line - GSM4105719 ATL2_EZH1 cell type:ATL patient PBMC - GSM4105783 TL-Om1_shCtrl_SUZ12 cell type:ATL cell line - GSM4105719 ATL2_EZH1 cell type:ATL patient PBMC - GSM4105720 ATL2_EZH2 cell type:ATL patient PBMC - GSM4105783 TL-Om1_shCtrl_SUZ12 cell type:ATL cell line - GSM4105784 MCF7_EZH2WT_FLAG cell type:Breast cancer cell line - GSM4105784 MCF7_EZH2WT_FLAG cell type:Breast cancer cell line - GSM4105785 MCF7_EZH2Y641F_FLAG cell type:Breast cancer cell line - GSM4105785 MCF7_EZH2Y641F_FLAG cell type:Breast cancer cell line - GSM4105786 MCF7_EZH2EZH1_FLAG cell type:Breast cancer cell line - GSM4105720 ATL2_EZH2 cell type:ATL patient PBMC - GSM4105786 MCF7_EZH2EZH1_FLAG cell type:Breast cancer cell line - GSM4105787 MCF7_EZH2WT_EZH1 cell type:Breast cancer cell line - GSM4105742 TL-Om1_shEZH1_2_EZH1 cell type:ATL cell line - GSM4105787 MCF7_EZH2WT_EZH1 cell type:Breast cancer cell line - GSM4105788 MCF7_EZH2Y641F_EZH1 cell type:Breast cancer cell line - GSM4105742 TL-Om1_shEZH1_2_EZH1 cell type:ATL cell line - GSM4105788 MCF7_EZH2Y641F_EZH1 cell type:Breast cancer cell line - GSM4105743 TL-Om1_shEZH2_1_EZH1 cell type:ATL cell line - GSM4105721 ATL3_controlIgG cell type:ATL patient PBMC - GSM4105789 MCF7_EZH2EZH1_EZH1 cell type:Breast cancer cell line - GSM4105743 TL-Om1_shEZH2_1_EZH1 cell type:ATL cell line - GSM4105721 ATL3_controlIgG cell type:ATL patient PBMC - GSM4105789 MCF7_EZH2EZH1_EZH1 cell type:Breast cancer cell line - GSM4105744 TL-Om1_shEZH2_2_EZH1 cell type:ATL cell line - GSM4105722 ATL3_EZH1 cell type:ATL patient PBMC - GSM4105790 SUDHL8_DMSO_H3K27me3 cell type:DLBCL cell line - GSM4105744 TL-Om1_shEZH2_2_EZH1 cell type:ATL cell line - GSM4105722 ATL3_EZH1 cell type:ATL patient PBMC - GSM4105745 TL-Om1_shCtrl_EZH2 cell type:ATL cell line - GSM4105723 ATL3_EZH2 cell type:ATL patient PBMC - GSM4105745 TL-Om1_shCtrl_EZH2 cell type:ATL cell line - GSM4105723 ATL3_EZH2 cell type:ATL patient PBMC - GSM4105762 HUT102_DMSO_H3K27me3 cell type:HTLV-1 infected cell line - GSM4105763 HUT102_OR-S1_H3K27me3 cell type:HTLV-1 infected cell line - GSM4105763 HUT102_OR-S1_H3K27me3 cell type:HTLV-1 infected cell line - GSM4105790 SUDHL8_DMSO_H3K27me3 cell type:DLBCL cell line - GSM4105746 TL-Om1_shEZH1_1_EZH2 cell type:ATL cell line - GSM4105724 TL-Om1_DMSO_EZH1 cell type:ATL cell line - GSM4105791 SUDHL8_OR-S1_H3K27me3 cell type:DLBCL cell line - GSM4105724 TL-Om1_DMSO_EZH1 cell type:ATL cell line - GSM4105746 TL-Om1_shEZH1_1_EZH2 cell type:ATL cell line - GSM4105791 SUDHL8_OR-S1_H3K27me3 cell type:DLBCL cell line - GSM4105747 TL-Om1_shEZH1_2_EZH2 cell type:ATL cell line - GSM4105725 TL-Om1_GSK126_EZH1 cell type:ATL cell line - GSM4105747 TL-Om1_shEZH1_2_EZH2 cell type:ATL cell line - GSM4105725 TL-Om1_GSK126_EZH1 cell type:ATL cell line - GSM4105792 SUDHL8_DMSO_EZH1 cell type:DLBCL cell line - GSM4105726 TL-Om1_OR-S1_EZH1 cell type:ATL cell line - GSM4105792 SUDHL8_DMSO_EZH1 cell type:DLBCL cell line - GSM4105726 TL-Om1_OR-S1_EZH1 cell type:ATL cell line - GSM4105793 SUDHL8_OR-S1_EZH1 cell type:DLBCL cell line - GSM4105793 SUDHL8_OR-S1_EZH1 cell type:DLBCL cell line - GSM4105794 SUDHL8_DMSO_EZH2 cell type:DLBCL cell line - GSM4105818 MCF7_shCtrl_EZH2 cell type:Breast cancer cell line - GSM4105794 SUDHL8_DMSO_EZH2 cell type:DLBCL cell line - GSM4105748 TL-Om1_shEZH2_1_EZH2 cell type:ATL cell line - GSM4105795 SUDHL8_OR-S1_EZH2 cell type:DLBCL cell line - GSM4105727 TL-Om1_OR-S2_EZH1 cell type:ATL cell line - GSM4105819 MCF7_shARID1A_EZH2 cell type:Breast cancer cell line - GSM4105795 SUDHL8_OR-S1_EZH2 cell type:DLBCL cell line - GSM4105796 TL-Om1_DMSO_ARID1A cell type:ATL cell line - GSM4105819 MCF7_shARID1A_EZH2 cell type:Breast cancer cell line - GSM4105796 TL-Om1_DMSO_ARID1A cell type:ATL cell line - GSM4105797 TL-Om1_GSK126_ARID1A cell type:ATL cell line - GSM4105820 MCF7_shKDM6A_EZH2 cell type:Breast cancer cell line - GSM4105748 TL-Om1_shEZH2_1_EZH2 cell type:ATL cell line - GSM4105705 Normal1_controlIgG cell type:Normal CD4+ T-cell - GSM4105797 TL-Om1_GSK126_ARID1A cell type:ATL cell line - GSM4105798 TL-Om1_OR-S1_ARID1A cell type:ATL cell line - GSM4105820 MCF7_shKDM6A_EZH2 cell type:Breast cancer cell line - GSM4105798 TL-Om1_OR-S1_ARID1A cell type:ATL cell line - GSM4105799 TL-Om1_DMSO_BRG1 cell type:ATL cell line - GSM4105705 Normal1_controlIgG cell type:Normal CD4+ T-cell - GSM4105749 TL-Om1_shEZH2_2_EZH2 cell type:ATL cell line - GSM4105821 MCF7_shBAP1_EZH2 cell type:Breast cancer cell line - GSM4105706 Normal1_EZH1 cell type:Normal CD4+ T-cell - GSM4105749 TL-Om1_shEZH2_2_EZH2 cell type:ATL cell line - GSM4105799 TL-Om1_DMSO_BRG1 cell type:ATL cell line - GSM4105706 Normal1_EZH1 cell type:Normal CD4+ T-cell - GSM4105821 MCF7_shBAP1_EZH2 cell type:Breast cancer cell line - GSM4105800 TL-Om1_GSK126_BRG1 cell type:ATL cell line - GSM4105800 TL-Om1_GSK126_BRG1 cell type:ATL cell line - GSM4105801 TL-Om1_OR-S1_BRG1 cell type:ATL cell line - GSM4105801 TL-Om1_OR-S1_BRG1 cell type:ATL cell line - GSM4105707 Normal2_2_controlIgG cell type:Normal CD4+ T-cell - GSM4105802 LCL_shCtrl_EZH1 cell type:EBV infected LCL - GSM4105750 TL-Om1_shCtrl_DMSO_EZH1 cell type:ATL cell line - GSM4105802 LCL_shCtrl_EZH1 cell type:EBV infected LCL - GSM4105750 TL-Om1_shCtrl_DMSO_EZH1 cell type:ATL cell line - GSM4105751 TL-Om1_shCtrl_GSK126_EZH1 cell type:ATL cell line - GSM4105751 TL-Om1_shCtrl_GSK126_EZH1 cell type:ATL cell line - GSM4105752 TL-Om1_shYY1_DMSO_EZH1 cell type:ATL cell line - GSM4105752 TL-Om1_shYY1_DMSO_EZH1 cell type:ATL cell line - GSM4105803 LCL_shMLL2_EZH1 cell type:EBV infected LCL - GSM4105803 LCL_shMLL2_EZH1 cell type:EBV infected LCL - GSM4105753 TL-Om1_shYY1_GSK126_EZH1 cell type:ATL cell line - GSM4105804 LCL_shCtrl_EZH2 cell type:EBV infected LCL - GSM4105753 TL-Om1_shYY1_GSK126_EZH1 cell type:ATL cell line - GSM4105764 HUT102_DMSO_EZH1 cell type:HTLV-1 infected cell line - GSM4105754 DLCL2_DMSO_H3K27me3 cell type:DLBCL cell line - GSM4105764 HUT102_DMSO_EZH1 cell type:HTLV-1 infected cell line - GSM4105754 DLCL2_DMSO_H3K27me3 cell type:DLBCL cell line - GSM4105804 LCL_shCtrl_EZH2 cell type:EBV infected LCL - GSM4105765 HUT102_OR-S1_EZH1 cell type:HTLV-1 infected cell line - GSM4105805 LCL_shMLL2_EZH2 cell type:EBV infected LCL - GSM4105765 HUT102_OR-S1_EZH1 cell type:HTLV-1 infected cell line - GSM4105755 DLCL2_GSK126_H3K27me3 cell type:DLBCL cell line - GSM4105805 LCL_shMLL2_EZH2 cell type:EBV infected LCL - GSM4105766 HUT102_DMSO_EZH2 cell type:HTLV-1 infected cell line - GSM4105806 LCL_shCtrl_H3K27me3 cell type:EBV infected LCL - GSM4105755 DLCL2_GSK126_H3K27me3 cell type:DLBCL cell line - GSM4105806 LCL_shCtrl_H3K27me3 cell type:EBV infected LCL - GSM4105766 HUT102_DMSO_EZH2 cell type:HTLV-1 infected cell line - GSM4105807 LCL_shMLL2_H3K27me3 cell type:EBV infected LCL - GSM4105767 HUT102_OR-S2_EZH2 cell type:HTLV-1 infected cell line - GSM4105807 LCL_shMLL2_H3K27me3 cell type:EBV infected LCL - GSM4105808 LCL_shCtrl_H3K4me3 cell type:EBV infected LCL - GSM4105808 LCL_shCtrl_H3K4me3 cell type:EBV infected LCL - GSM4105809 LCL_shMLL2_H3K4me3 cell type:EBV infected LCL - GSM4105809 LCL_shMLL2_H3K4me3 cell type:EBV infected LCL - GSM4105810 MCF7_shCtrl_H3K27me3 cell type:Breast cancer cell line - GSM4105756 DLCL2_OR-S1_H3K27me3 cell type:DLBCL cell line - GSM4105810 MCF7_shCtrl_H3K27me3 cell type:Breast cancer cell line - GSM4105767 HUT102_OR-S2_EZH2 cell type:HTLV-1 infected cell line - GSM4105811 MCF7_shARID1A_H3K27me3 cell type:Breast cancer cell line - GSM4105768 TL-Om1_DMSO_RelA cell type:ATL cell line - GSM4105811 MCF7_shARID1A_H3K27me3 cell type:Breast cancer cell line - GSM4105812 MCF7_shKDM6A_H3K27me3 cell type:Breast cancer cell line - GSM4105756 DLCL2_OR-S1_H3K27me3 cell type:DLBCL cell line - GSM4105768 TL-Om1_DMSO_RelA cell type:ATL cell line - GSM4105812 MCF7_shKDM6A_H3K27me3 cell type:Breast cancer cell line - GSM4105813 MCF7_shBAP1_H3K27me3 cell type:Breast cancer cell line - GSM4105813 MCF7_shBAP1_H3K27me3 cell type:Breast cancer cell line - GSM4105814 MCF7_shCtrl_EZH1 cell type:Breast cancer cell line - GSM4105814 MCF7_shCtrl_EZH1 cell type:Breast cancer cell line - GSM4105815 MCF7_shARID1A_EZH1 cell type:Breast cancer cell line - GSM4105815 MCF7_shARID1A_EZH1 cell type:Breast cancer cell line - GSM4105816 MCF7_shKDM6A_EZH1 cell type:Breast cancer cell line - GSM4105816 MCF7_shKDM6A_EZH1 cell type:Breast cancer cell line - GSM4105817 MCF7_shBAP1_EZH1 cell type:Breast cancer cell line - GSM4105817 MCF7_shBAP1_EZH1 cell type:Breast cancer cell line - GSM4105757 DLCL2_OR-S2_H3K27me3 cell type:DLBCL cell line - GSM4105818 MCF7_shCtrl_EZH2 cell type:Breast cancer cell line - GSM4105769 TL-Om1_OR-S1_RelA cell type:ATL cell line - GSM4105769 TL-Om1_OR-S1_RelA cell type:ATL cell line - GSM4105757 DLCL2_OR-S2_H3K27me3 cell type:DLBCL cell line - GSM4105770 TL-Om1_DMSO_RelB cell type:ATL cell line - GSM4105770 TL-Om1_DMSO_RelB cell type:ATL cell line - GSM4105758 DLCL2_DMSO_EZH1 cell type:DLBCL cell line - GSM4105771 TL-Om1_OR-S1_RelB cell type:ATL cell line - GSM4105758 DLCL2_DMSO_EZH1 cell type:DLBCL cell line - GSM4105771 TL-Om1_OR-S1_RelB cell type:ATL cell line - GSM4105772 TL-Om1_DMSO_H2AK119ub cell type:ATL cell line - GSM4105759 DLCL2_GSK126_EZH1 cell type:DLBCL cell line - GSM4105772 TL-Om1_DMSO_H2AK119ub cell type:ATL cell line - GSM4105759 DLCL2_GSK126_EZH1 cell type:DLBCL cell line - GSM4105773 TL-Om1_OR-S1_H2AK119ub cell type:ATL cell line - GSM4105773 TL-Om1_OR-S1_H2AK119ub cell type:ATL cell line - GSM4105760 DLCL2_OR-S1_EZH1 cell type:DLBCL cell line - GSM4105774 TL-Om1_DMSO_RNApolII cell type:ATL cell line - GSM4105760 DLCL2_OR-S1_EZH1 cell type:DLBCL cell line - GSM4105774 TL-Om1_DMSO_RNApolII cell type:ATL cell line - GSM4105775 TL-Om1_OR-S1_RNApolII cell type:ATL cell line - GSM4105761 DLCL2_OR-S2_EZH1 cell type:DLBCL cell line - GSM4105775 TL-Om1_OR-S1_RNApolII cell type:ATL cell line - GSM4105776 TL-Om1_DMSO_H3K27ac cell type:ATL cell line - GSM4105761 DLCL2_OR-S2_EZH1 cell type:DLBCL cell line - GSM4105776 TL-Om1_DMSO_H3K27ac cell type:ATL cell line - GSM4105762 HUT102_DMSO_H3K27me3 cell type:HTLV-1 infected cell line - GSM4105777 TL-Om1_OR-S1_H3K27ac cell type:ATL cell line - GSM4105777 TL-Om1_OR-S1_H3K27ac cell type:ATL cell line - GSM4105778 TL-Om1_shEZH1_SUZ12 cell type:ATL cell line - GSM4105778 TL-Om1_shEZH1_SUZ12 cell type:ATL cell line - GSM4105779 TL-Om1_shEZH2_SUZ12 cell type:ATL cell line - GSM4105779 TL-Om1_shEZH2_SUZ12 cell type:ATL cell line - GSM4105780 TL-Om1_shCtrl_H3K27me3 cell type:ATL cell line - GSM4105780 TL-Om1_shCtrl_H3K27me3 cell type:ATL cell line - GSM4105781 TL-Om1_shEZH1_H3K27me3 cell type:ATL cell line -
Platform	GPL19784  : Agilent-027954 SurePrint G3 Human Promoter Microarray 2x400K [Probe Name version]
Literature	31747604