|
| Status |
Public on May 29, 2019 |
| Title |
Selective Disruption of Core Regulatory Transcription [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Activation of identity determining transcription factors (TFs), or core regulatory TFs, is governed by cell-type specific enhancers, an important subset of these being super enhancers (SEs). This mechanism is distinct from constitutive expression of housekeeping genes. The characterization of drug-like small molecules to selectively inhibit core regulatory circuitry is of high interest for treatment of cancers, which are addicted to core regulatory TF function at SEs. Surprisingly, we find histone deacetylases (HDAC) to be an indispensable component of SE-driven transcription. While histone acetylation is a marker for active genes, over accumulation of acetylation selectively halts core regulatory transcription. We show this conundrum may in part be explained by a SE-specific need for resetting histones to maintain SE boundaries, to facilitate enhancer-promoter looping and high levels of transcription.
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| |
|
| Overall design |
RNA-seq data for FP-RMS cells treated with various concentrations of various small molecules modulators of epigenetic processes.
|
| |
|
| Contributor(s) |
Gryder BE, Wen X, Khan J |
| Citation(s) |
31285436 |
| |
| Submission date |
Oct 10, 2018 |
| Last update date |
Aug 28, 2019 |
| Contact name |
Ashish Lal |
| E-mail(s) |
ashish.lal@nih.gov
|
| Phone |
2407607396
|
| Organization name |
NCI, NIH
|
| Department |
Genetics Branch
|
| Lab |
Javed Khan
|
| Street address |
37 Convent Dr.
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (56)
|
|
| This SubSeries is part of SuperSeries: |
| GSE120771 |
Selective Disruption of Core Regulatory Transcription |
|
| Relations |
| BioProject |
PRJNA495665 |
| SRA |
SRP164953 |
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