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Status |
Public on Oct 03, 2019 |
Title |
Epigenetic pattern after EZH1,2 inhibition in lymohoma cells |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by genome tiling array
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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.
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Overall design |
We explored epigenome (EZH1/2 occupancies and histone modifications) in aggressive lymphoma samples and cell lines treated with EZH1/2 inhibitors by using ChIP-on-chip platform
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Contributor(s) |
Yamagishi M, Hori M, Fujikawa D |
Citation(s) |
31747604 |
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Submission date |
Oct 02, 2019 |
Last update date |
Nov 27, 2019 |
Contact name |
Makoto Yamagishi |
E-mail(s) |
[email protected]
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Organization name |
The University of Tokyo
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Lab |
Lab. Tumor Cell Biology
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Street address |
4-6-1, Shirokanedai
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City |
Minato-ku |
State/province |
Tokyo |
ZIP/Postal code |
108-8639 |
Country |
Japan |
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Platforms (1) |
GPL19784 |
Agilent-027954 SurePrint G3 Human Promoter Microarray 2x400K [Probe Name version] |
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Samples (117)
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Relations |
BioProject |
PRJNA575541 |
Supplementary file |
Size |
Download |
File type/resource |
GSE138342_Matrix_data_10_DLCL2_EZHi_H3K27me3_Coc.xlsx |
22.3 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_11_DLCL2_EZHi_EZH1_Coc.xlsx |
18.7 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_12_HUT102_OR-S1_H3K27me3_Coc.xlsx |
16.9 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_13_HUT102_OR-S1_EZH1_Coc.xlsx |
16.7 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_14_HUT102_OR-S1_EZH2_Coc.xlsx |
18.3 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_15_TL-Om1_OR-S1_RelA_Coc.xlsx |
14.0 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_16_TL-Om1_OR-S1_RelB_Coc.xlsx |
13.9 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_17_TL-Om1_OR-S1_H2AK119ub_Coc.xlsx |
18.0 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_18_TL-Om1_OR-S1_RNAPolII_Coc.xlsx |
18.3 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_19_TL-Om1_OR-S1_H3K27ac_Coc.xlsx |
18.7 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_1_Normal__ATL_EZH1_Coc.xlsx |
37.6 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_20_TL-Om1_shEZH1_2_H3K27me3_Coc.xlsx |
20.3 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_21_TL-Om1_shEZH1_2_SUZ12_Coc.xlsx |
22.6 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_22_MCF7_EZH1_2_OE_FLAG_Coc.xlsx |
20.7 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_23_MCF7_EZH1_2_OE_EZH1_Coc.xlsx |
20.8 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_24_SUDHL8_OR-S1_H3K27me3_Coc.xlsx |
18.6 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_25_SUDHL8_OR-S1_EZH1_Coc.xlsx |
18.4 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_26_SUDHL8_OR-S1_EZH2_Coc.xlsx |
18.1 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_27_TL-Om1_EZHi_ARID1A_Coc.xlsx |
20.6 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_28_TL-Om1_EZHi_BRG1_Coc.xlsx |
20.5 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_29_LCL_shMLL2_EZH1_Coc.xlsx |
18.2 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_2_Normal__ATL_EZH2_Coc.xlsx |
58.4 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_30_LCL_shMLL2_EZH2_Coc.xlsx |
18.3 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_31_LCL_shMLL2_H3K27me3_Coc.xlsx |
18.4 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_32_LCL_shMLL2_H3K4me3_Coc.xlsx |
17.1 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_33_MCF7_shBAF_H3K27me3_Coc.xlsx |
23.9 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_34_MCF7_shBAF_EZH1_Coc.xlsx |
23.4 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_35_MCF7_shBAF_EZH2_Coc.xlsx |
23.5 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_3_TL-Om1_EZHi_EZH1_Coc.xlsx |
21.5 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_4_TL-Om1_EZHi_EZH2_Coc.xlsx |
20.9 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_5_TL-Om1_EZHi_YY1_Coc.xlsx |
21.5 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_6_TL-Om1_EZHi_H3K4me3_Coc.xlsx |
21.5 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_7_TL-Om1_shEZH1_2_EZH1_Coc.xlsx |
20.8 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_8_TL-Om1_shEZH1_2_EZH2_Coc.xlsx |
21.7 Mb |
(ftp)(http) |
XLSX |
GSE138342_Matrix_data_9_TL-Om1_shYY1_GSK126_EZH1_Coc.xlsx |
20.3 Mb |
(ftp)(http) |
XLSX |
GSE138342_RAW.tar |
5.0 Gb |
(http)(custom) |
TAR (of TXT) |
Processed data are available on Series record |