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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 22, 2024 |
| Title |
Transcription factor network dynamics during the commitment to oncogene-induced senescence [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Aberrant oncogenic signaling causes cells to transition into oncogene-induced senescence (OIS) to limit uncontrolled proliferation. Despite being a potent tumor suppressor mechanism, OIS is an unstable cell state susceptible to reprogramming that can promote tumorigenesis. Therefore, elucidating the underlying gene regulatory mechanisms that commit cells to OIS is critical to identifying actionable targets to modulate the senescence state. We previously showed that timely execution of the OIS program is governed by hierarchical transcription factor (TF) networks. However, the gene regulatory mechanisms that prime cells to commit to the OIS fate early upon oncogene hyperactivation are currently not known. Here, we leveraged our time-resolved multi-omic profiling approach to generate TF networks during the first 24 h of oncogenic HRASG12V activation. Using this approach, we demonstrate that the commitment to OIS requires the rearrangement of the TF network on a pre-established epigenomic landscape, priming the cells for the substantial chromatin remodeling that underpins the transition to OIS. Our results provide a detailed map of the chromatin landscape before cells transition to OIS thus offering a platform for manipulation of senescence outcomes of potentially therapeutic value.
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| Overall design |
RNA seq of WI38-ER:RAS(G12V) cells collected at indicated time-points post induction of oncogenic HRAS(G12V) with 4-hydroxy tamoxifen (4-OHT) treatment.
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| Contributor(s) |
Vasilopoulos T, Martínez Zamudio RI |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jul 03, 2024 |
| Last update date |
Jul 23, 2024 |
| Contact name |
Ricardo Iván Martínez Zamudio |
| E-mail(s) |
rm1238@rwjms.rutgers.edu
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| Organization name |
Rutgers Biomedical and Health Sciences | Rutgers-Robert Wood Johnson Medical School
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| Department |
Pharmacology
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| Lab |
Martínez Zamudio Lab
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| Street address |
675 Hoes Lane West
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| City |
Piscataway |
| State/province |
New Jersey |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (1) |
| GPL34281 |
Illumina NovaSeq X (Homo sapiens) |
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| Samples (12)
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| GSM8377550 |
WI38-ER:RASG12V, 2hrs post-treament with EtOH, Biol Rep1 |
| GSM8377551 |
WI38-ER:RASG12V, 2hrs post-treament with 4-OHT, Biol Rep1 |
| GSM8377552 |
WI38-ER:RASG12V, 4hrs post-treament with 4-OHT, Biol Rep1 |
| GSM8377553 |
WI38-ER:RASG12V, 12hrs post-treament with 4-OHT, Biol Rep1 |
| GSM8377554 |
WI38-ER:RASG12V, 24hrs post-treament with 4-OHT, Biol Rep1 |
| GSM8377555 |
WI38-ER:RASG12V, 144hrs post-treament with 4-OHT, Biol Rep1 |
| GSM8377556 |
WI38-ER:RASG12V, 2hrs post-treament with EtOH, Biol Rep2 |
| GSM8377557 |
WI38-ER:RASG12V, 2hrs post-treament with 4-OHT, Biol Rep2 |
| GSM8377558 |
WI38-ER:RASG12V, 4hrs post-treament with 4-OHT, Biol Rep2 |
| GSM8377559 |
WI38-ER:RASG12V, 12hrs post-treament with 4-OHT, Biol Rep2 |
| GSM8377560 |
WI38-ER:RASG12V, 24hrs post-treament with 4-OHT, Biol Rep2 |
| GSM8377561 |
WI38-ER:RASG12V, 144hrs post-treament with 4-OHT, Biol Rep2 |
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| Relations |
| BioProject |
PRJNA1131472 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE271461_Early_OIS_all_timepoints_counts_29-III-2024.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
| GSE271461_RAW.tar |
421.3 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
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