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Series GSE89688 Query DataSets for GSE89688
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
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.
 
Overall design ChIP-seq analysis of CREBBP bound regions and H3K27Ac in purified human germinal center B cells.
 
Contributor(s) Pasaqualucci L, Holmes AB, Dalla-Favera R
Citation(s) 28069569
Submission date Nov 09, 2016
Last update date May 15, 2019
Contact name Laura Pasqualucci
E-mail(s) lp171@cumc.columbia.edu
Organization name Columbia University
Department Institute for Cancer Genetics
Street address 1130 St Nicholas Avenue
City New York
State/province NY
ZIP/Postal code 10032
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (6)
GSM2386720 CB4_H3K27Ac
GSM2386721 CB4_CREBBP
GSM2386722 CB5_H3K27Ac
Relations
BioProject PRJNA352949
SRA SRP093282

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Supplementary file Size Download File type/resource
GSE89688_RAW.tar 960.0 Kb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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