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| Status |
Public on Sep 18, 2024 |
| Title |
An eRNA Transcription Checkpoint For Diverse Signal-dependent Enhancer Activation Programs [ATAC-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The evidence that several signal and ligand-dependent pathways function by activating regulatory enhancer programs suggests that a “checkpoint” strategy may underline activation of some or even many diversely-regulated enhancers. Here, we report a molecular mechanism common to several acute signal- and ligand-dependent enhancer activation programs based on release of a shared eRNA transcription checkpoint. This requires recruitment of a DNA-PKcs-phosphorylated RING finger repressor, KAP1, functioning as a modulator, inhibiting its association with 7SK and E3 SUMO ligase activity on the CDK9 subunit of P-TEFb, facilitating formation of an activated P-TEFb complex, licensing eRNA elongation. Overcoming this checkpoint for signal-dependent enhancer activation occurs in diverse pathways including estrogen receptor α, NF-κB-regulated proinflammatory, androgen receptor and neuronal depolarization. Therefore, a specific strategy required to convert a basal state enhancer P-TEFb complex to an active state to release a conserved checkpoint is apparently employed by several functionally-important signal/ligand-regulated regulatory enhancers to implement the instructions of endocrine/paracrine system.
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| Overall design |
For hormone treatments, cells were incubated at 37°C and 5% CO2 for at least 3 days in phenol red-free DMEM (GIBCO/Invitrogen) supplemented with 5% charcoal dextran-stripped FBS (GIBCO/Invitrogen). 17-β-Estradiol (E2; Steraloids, Inc.) was added to a final concentration of 100 nM. For knock-down of KAP1 genes, the shRNA were employed.
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| Citation missing |
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| Submission date |
Sep 17, 2024 |
| Last update date |
Sep 19, 2024 |
| Contact name |
Lishuan Wang |
| E-mail(s) |
weiyuan1220@gmail.com
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| Phone |
6262054087
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| Organization name |
UCSD
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| Lab |
Rosenfeld, Michael
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| Street address |
9500 Gilman Drive
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| City |
SAN DIEGO |
| State/province |
California |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA1162080 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE277381_RAW.tar |
94.6 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
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