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| Status |
Public on Feb 08, 2017 |
| Title |
Hotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
We sought to identify hotspots of aberrant enhancer activity in colorectal cancer (CRC) through interrogation of the enhancer epigenomes of a large cohort of genetically diverse CRC samples and normal colonic crypts, representing the cell type of origin for CRC. Through characterization of loci that exhibit differential enhancer activity, we identified sets of enhancers that are recurrently commissioned and decommissioned in CRC relative to normal crypts. The set of recurrently commissioned, or “acquired”, enhancers are of particular interest. Many originate from primed chromatin and activate known and potentially novel oncogenes in CRC. They are also frequently constituents of super enhancers and loaded with AP-1 and cohesin complex proteins. Nearly half of all GWAS CRC risk loci identified to date map to these enhancer hotspots. Through functional studies and integrative analyses we further demonstrate that CRC growth can be mitigated through pharmacologic inhibition or targeted knockout of genes activated by recurrent enhancers.
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| Overall design |
H3K27ac profiles in 28 CRC cell lines, 4 primary CRC specimens, and 4 normal colon crypt samples; H3K4me1 profiles in 27 CRC cell lines, 4 primary CRCs, and 4 crypt samples; H3K27me3 profiles in 1 CRC cell line and 1 crypt sample; DNase hypersensitivity site profiles in 3 CRC cell lines and 3 crypt samples; and associated input DNA. Gene expression profiles for 6 CRC cell lines without treatment and at 4 time points of treatments with JQ1.
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| |
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| Contributor(s) |
Cohen AJ, Saiakhova AR, Scacheri PC |
| Citation(s) |
28169291 |
| Submission date |
Feb 09, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter Scacheri |
| E-mail(s) |
pxs183@case.edu
|
| Phone |
216-368-3458
|
| Organization name |
Case Western Reserve University
|
| Street address |
10900 Euclid Ave; BRB 647
|
| City |
Cleveland Heights |
| State/province |
OH |
| ZIP/Postal code |
44106 |
| Country |
USA |
| |
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| Platforms (3) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
| GPL15456 |
Illumina HiScanSQ (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (139)
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| Relations |
| BioProject |
PRJNA311329 |
| SRA |
SRP069828 |
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