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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 11, 2017 |
| Title |
Identification of CREBBP bound genes in germinal center B cells |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Inactivating mutations of the gene encoding for the CREBBP acetyltransferase are highly frequent in diffuse large B cell lymphoma (DLBCL, 30% of cases) and follicular lymphoma (FL, 60% of cases), the two most common cancers derived from the germinal-center (GC). However, the role of CREBBP inactivation in lymphomagenesis remains unclear. Using functional epigenomics and mouse genetics, here we define the program modulated by CREBBP in primary human GC B cells and show that CREBBP regulates enhancer/super-enhancer networks, with specific roles in GC/post-GC cell fate decisions. Conditional GC-specific deletion of Crebbp in the mouse perturbs the expression of a limited set of genes involved in the regulation of signal transduction (BCR, TLR and CD40), lineage specification (NF-κB and BCL6) and terminal B cell differentiation (PRDM1, IRF4). Consistently, Crebbp-deficient B cells exhibit proliferative advantage and show impaired plasma cell differentiation. While GC-specific loss of Crebbp was not sufficient to initiate malignant transformation, compound Crebbp-haploinsufficient/BCL2-transgenic mice, mimicking the genetics ofFL and DLBCL, display an increased incidence of clonal lymphoid malignancies recapitulating the features of the human diseases. These findings establish CREBBPas a haploinsufficient tumor suppressor gene in GC B cells and provide insights into the mechanisms and targets by which loss of CREBBP contributes to lymphomagenesis.
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| Overall design |
ChIP-seq analysis of CREBBP bound regions and H3K27Ac in purified human germinal center B cells.
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| Contributor(s) |
Pasqualucci L, Holmes AB, Dalla-Favera R |
| Citation(s) |
28069569 |
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| Submission date |
Nov 09, 2016 |
| Last update date |
Feb 23, 2023 |
| Contact name |
Laura Pasqualucci |
| E-mail(s) |
lp171@cumc.columbia.edu
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| Organization name |
Columbia University
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| Department |
Institute for Cancer Genetics
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| Street address |
1130 St Nicholas Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA352949 |
| SRA |
SRP093282 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE89688_RAW.tar |
960.0 Kb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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