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EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation

UID: 10544

Summary from the GEO: "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.
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."
Subject of Study
OncoTree Cancer Type(s)
B-Cell Prolymphocytic Leukemia
Diffuse Large B-Cell Lymphoma, NOS
Germinal Center B-Cell Type
Lymphoid Neoplasm
Mature B-Cell Neoplasms
Access via GEO

BED, TXT, and WIG Sequencing Data.
Accession #: GSE45982

Access via SRA

61 ChIP and RNA Sequences.
Accession #: SRP021509

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA198866

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Data Type
Equipment Used
Illumina HiSeq 2000
Dataset Format(s)
Plain Text, SRA, BED, BIGWIG
Dataset Size
6.6 Gb (TAR (of BED, TXT, WIG), 214.7 Gb (SRA)
Data Catalog Record Updated