GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
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
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
GSM2386722 CB5_H3K27Ac
BioProject PRJNA352949
SRA SRP093282

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap