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Series GSE45982 Query DataSets for GSE45982
Status Public on May 13, 2013
Title EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B-cells and targeted by somatic mutations in B-cell lymphomas. Here we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions in mice. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B-cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets in B-cells, and in human B-cell lymphomas. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GCB-type DLBCLs are mostly addicted to EZH2, regardless of mutation status, but not the more differentiated ABC-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting.
Overall design RNA sequencing and H3K27me3 ChIP sequencing of human DLBCL cell lines and murine BCL1 cell line. RNA sequencing, H3K27me3 and H3K4me3 ChIP sequencing of B cells from de-identified human tonsills.
Contributor(s) B├ęguelin W, Teater M, Elemento O, Melnick AM
Citation(s) 23680150, 26521025
Submission date Apr 11, 2013
Last update date Mar 30, 2020
Contact name Matt Teater
Organization name Weill Cornell Medical College
Street address 445 E 69th St
City New York
State/province NY
ZIP/Postal code 10021
Country USA
Platforms (3)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (61)
GSM1129307 OCI-Ly7 GSK343
GSM1129308 OCI-Ly7 GSK669
GSM1129309 Farage GSK343
BioProject PRJNA198866
SRA SRP021509

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Supplementary file Size Download File type/resource
GSE45982_RAW.tar 6.6 Gb (http)(custom) TAR (of BED, TXT, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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