|
| Status |
Public on Jan 23, 2015 |
| Title |
CDK7-dependent Transcriptional Addition in Basal-like Breast Cancer (ChIP-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Basal-like breast cancer (BBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that BBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing a novel kinase inhibitor and CRISPR/Cas9-mediated gene editing, we show here that basal but not luminal breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. BBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An “Achilles cluster” of BBC-specific genes are extremely sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in BBC and CDK7 inhibition may be useful therapy for this challenging cancer.
|
| |
|
| Overall design |
ChIP-Seq for H3K27ac in basal-like breast cancer and luminal-like breast cancer cell lines
|
| |
|
| Contributor(s) |
Wang Y, Kwiatkowski N, Abraham BJ, Lee TI, Zhao J, Young RA, Gray NS |
| Citation(s) |
26406377 |
| Submission date |
Jan 22, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard A Young |
| E-mail(s) |
young_computation@wi.mit.edu
|
| Phone |
617-258-5219
|
| Organization name |
Whitehead Institute for Biomedical Research
|
| Lab |
Young Lab
|
| Street address |
9 Cambridge Center
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (8)
|
|
| This SubSeries is part of SuperSeries: |
| GSE69107 |
CDK7-dependent Transcriptional Addiction in Basal-like Breast Cancer |
|
| Relations |
| BioProject |
PRJNA273393 |
| SRA |
SRP052748 |
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