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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 05, 2023 |
| Title |
Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Although oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells can escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors for escape from OIS and identify ‘senescence-associated chromatin scars (SACS)’ as an epigenetic memory of OIS, detectable during colorectal cancer progression. POU2F2 levels are elevated already in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory elements are associated with decreased patient survival. Our results support a model in which POU2F2 exploits a precoded enhancer landscape to promote senescence escape and reveal POU2F2 gene signatures and SACS as valuable biomarkers with diagnostic and prognostic potential.
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| Overall design |
Timeseries Assay for transposase accessible chromatin followed by sequencing (ATAC-seq) in GM21 human skin fibroblasts entering and exiting RAS-induced oncogene-induced senescence
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| Contributor(s) |
Zamudio RI, Stefa A, Freitas JA, Vasilopoulos T, Simpson M, Doré G, Roux P, Galan MA, Chokshi RJ, Bischof O, Herbig U |
| Citation(s) |
37082139 |
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| Submission date |
Jun 17, 2022 |
| Last update date |
May 12, 2023 |
| 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) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (25)
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| GSM6253122 |
GM21 fibroblasts, empty vector, day 32 post-transduction rep1 |
| GSM6253123 |
GM21 fibroblasts, empty vector, day 32 post-transduction rep2 |
| GSM6253124 |
GM21 fibroblasts, empty vector, day 56 post-transduction rep1 |
| GSM6253125 |
GM21 fibroblasts, empty vector, day 56 post-transduction rep2 |
| GSM6253126 |
GM21 fibroblasts, empty vector, day 8 post-transduction rep1 |
| GSM6253127 |
GM21 fibroblasts, empty vector, day 8 post-transduction rep2 |
| GSM6253128 |
GM21 fibroblasts, empty vector, day 8 post-transduction rep3 |
| GSM6253129 |
GM21 fibroblasts, empty vector, day 8 post-transduction rep4 |
| GSM6253130 |
GM21 fibroblasts, RAS overexpression, day 14 post-transduction rep1 |
| GSM6253131 |
GM21 fibroblasts, RAS overexpression, day 14 post-transduction rep2 |
| GSM6253132 |
GM21 fibroblasts, RAS overexpression, day 18 post-transduction rep1 |
| GSM6253133 |
GM21 fibroblasts, RAS overexpression, day 18 post-transduction rep2 |
| GSM6253134 |
GM21 fibroblasts, RAS overexpression, day 23 post-transduction rep1 |
| GSM6253135 |
GM21 fibroblasts, RAS overexpression, day 23 post-transduction rep2 |
| GSM6253136 |
GM21 fibroblasts, RAS overexpression, day 23 post-transduction rep3 |
| GSM6253137 |
GM21 fibroblasts, RAS overexpression, day 23 post-transduction rep4 |
| GSM6253138 |
GM21 fibroblasts, RAS overexpression, day 32 post-transduction rep1 |
| GSM6253139 |
GM21 fibroblasts, RAS overexpression, day 32 post-transduction rep2 |
| GSM6253140 |
GM21 fibroblasts, RAS overexpression, day 45 post-transduction rep1 |
| GSM6253141 |
GM21 fibroblasts, RAS overexpression, day 45 post-transduction rep2 |
| GSM6253142 |
GM21 fibroblasts, RAS overexpression, day 56 post-transduction rep1 |
| GSM6253143 |
GM21 fibroblasts, RAS overexpression, day 56 post-transduction rep2 |
| GSM6253144 |
GM21 fibroblasts, RAS overexpression, day 8 post-transduction rep1 |
| GSM6253145 |
GM21 fibroblasts, RAS overexpression, day 8 post-transduction rep2 |
| GSM6253146 |
GM21 fibroblasts, RAS overexpression, day 8 post-transduction rep3 |
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| This SubSeries is part of SuperSeries: |
| GSE206496 |
Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars |
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| Relations |
| BioProject |
PRJNA850441 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE206402_RAW.tar |
7.6 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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