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Expression profiling by high throughput sequencing

UID: 10689

Author(s): Jiang, Yanwen, Geng, Huimin, Melnick, Ari M.

Description
Summary from the GEO: "KD of CREBBP at lymphoma cell line, MD901, results in reduced expression. Genome-wide profiling of total RNA transcript levels in human cell line MD901 (CREBBP wild type) with shCREBBP and scramble control."

The associated article further explains the study and shows how the dataset is connected:

"Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates the development of germinal center (GC)–derived lymphomas in mice. In both human and murine lymphomas, CREBBP loss-of-function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses, including class II MHC. Mechanistically, CREBBP-regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we found to bind extensively to MHC class II loci. HDAC3 loss-of-function rescued repression of these enhancers and corresponding genes, including MHC class II, and more profoundly suppressed CREBBP -mutant lymphomas in vitro and in vivo. Hence, CREBBP loss-of-function contributes to lymphomagenesis by enabling unopposed suppression of enhancers by BCL6/SMRT/HDAC3 complexes, suggesting HDAC3-targeted therapy as a precision approach for CREBBP -mutant lymphomas. SIGNIFICANCE: Our fi ndings establish the tumor suppressor function of CREBBP in GC lymphomas in which CREBBP mutations disable acetylation and result in unopposed deacetylation by BCL6/SMRT/ HDAC3 complexes at enhancers of B-cell signaling and immune response genes. Hence, inhibition of HDAC3 can restore the enhancer histone acetylation and may serve as a targeted therapy for CREBBP - mutant lymphomas."
Subject of Study
Homo sapiens
Subject(s)
Lymphoma
OncoTree Cancer Type(s)
Lymphoid
Access via GEO

RNA sequencing data
Accession #: GSE79684

Access via SRA

RNA Sequence reads for 12 samples.
Accession #: SRP072506

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA316707

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Jiang Y, Ortega-Molina A, Geng H, et al. CREBBP inactivation promotes the development of HDAC3-dependent lymphomas. Cancer Discovery. 2017; 7(1):38-53.
Data Type
Genomic
Equipment Used
Illumina HiSeq 2000

High throughput gene sequencing system

Dataset Format(s)
SRA, XLSX
Dataset Size
3.3 Mb (XLSX), 22.8 Gb (SRA)
Data Catalog Record Updated
2023-12-07