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| Status |
Public on May 07, 2024 |
| Title |
KAP1 negatively regulates elongation kinetics to activate signal-induced transcription [PRO-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction are still unfolding. By combining an acute depletion system with high resolution genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Unexpectedly, acute KAP1 loss triggers an increase in RNA Polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation and dampening IEG transcription. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.
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| Overall design |
Comparative Active RNA Polymerase II density profiling analysis of PRO-Seq data for control (DMSO) and KAP1 depletion (dTAG) with and without serum (0, 5, 10 min)
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| Contributor(s) |
Hyder U, Nandu T, Thornton M, D'Orso I, Kraus WL |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 06, 2024 |
| Last update date |
May 07, 2024 |
| Contact name |
Ivan D'Orso |
| E-mail(s) |
ivan.dorso@utsouthwestern.edu
|
| Phone |
214-633-1374
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| Organization name |
UT Southwestern Medical Center
|
| Department |
Microbiology
|
| Lab |
NL3.110A
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| Street address |
5323 Harry Hines
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9048 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE246218 |
KAP1 regulates elongation kinetics to activate signal-induced transcription |
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| Relations |
| BioProject |
PRJNA1108276 |
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