|
| Status |
Public on Nov 21, 2016 |
| Title |
ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice [HCT116_RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Genes encoding subunits of SWI/SNF chromatin remodeling complexes are collectively mutated in ~20% of all human cancers. Although ARID1A is the most frequent target of mutations, the mechanism by which its inactivation promotes tumorigenesis is unclear. Here, we demonstrate that Arid1a functions as a tumor suppressor in the mouse colon, but not the small intestine, and that invasive ARID1A-deficient adenocarcinomas resemble human colorectal cancer (CRC). These tumors lack deregulation of APC/beta-catenin, crucial gatekeepers in common forms of intestinal cancer. ARID1A normally targets SWI/SNF complexes to enhancers, where they function in coordination with transcription factors (TFs) to facilitate gene activation. ARID1B preserves SWI/SNF function in ARID1A-deficient cells, but defects in SWI/SNF targeting and control of enhancer activity cause extensive dysregulation of gene expression. These findings represent an advance in colon cancer modeling and implicate enhancer-mediated gene regulation as a principal tumor suppressor function of ARID1A.
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| |
|
| Overall design |
RNA-seq in HCT116 colorectal cancer line for ARID1A WT, and Homozygous and Heterozygous KO cells.
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| |
|
| Contributor(s) |
Mathur R, Alver BH, Park PJ, Roberts CW |
| Citation(s) |
27941798 |
| |
| Submission date |
Jul 29, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter J Park |
| E-mail(s) |
peter_park@harvard.edu
|
| Phone |
617-432-7373
|
| Organization name |
Harvard Medical School
|
| Department |
Center for Biomedical Informatics
|
| Street address |
10 Shattuck St
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (6)
|
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| This SubSeries is part of SuperSeries: |
| GSE71514 |
ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice |
|
| Relations |
| BioProject |
PRJNA291422 |
| SRA |
SRP061776 |
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