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| 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.
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| 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.
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| Contributor(s) |
Béguelin 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 |
| E-mail(s) |
mrt2001@med.cornell.edu
|
| Organization name |
Weill Cornell Medical College
|
| Street address |
445 E 69th St
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
| |
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| Platforms (3) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (61)
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| Relations |
| BioProject |
PRJNA198866 |
| SRA |
SRP021509 |
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