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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 [ChIP-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 chromatin Immunoprecipitation DNA sequencing (ChIP-seq) of histone modifications H3K4me1 and H3K27ac in GM21 human skin fibroblasts entering and exiting RAS-induced oncogene-induced senescence
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| Contributor(s) |
Zamudio RI, Stefa A, Nabuco 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 11, 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 (30)
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| GSM6235098 |
GM21, Day 0, Rep 1, K27ac, ActiveMotif |
| GSM6235099 |
GM21, Day 0, Rep 2, K27ac, ActiveMotif |
| GSM6235100 |
GM21, Day 0, Rep 1, K4me1, ActiveMotif |
| GSM6235101 |
GM21, Day 0, Rep 2, K4me1, ActiveMotif |
| GSM6235102 |
GM21, Day 0, Rep 1, input |
| GSM6235103 |
GM21, Day 0, Rep 2, input |
| GSM6235104 |
GM21, Day 10, Rep 1, K27ac, ActiveMotif |
| GSM6235105 |
GM21, Day 10, Rep 2, K27ac, ActiveMotif |
| GSM6235106 |
GM21, Day 10, Rep 1, K4me1, ActiveMotif |
| GSM6235107 |
GM21, Day 10, Rep 2, K4me1, ActiveMotif |
| GSM6235108 |
GM21, Day 10, Rep 1, input |
| GSM6235109 |
GM21, Day 10, Rep 2, input |
| GSM6235110 |
GM21, Day 18, Rep 1, K27ac, ActiveMotif |
| GSM6235111 |
GM21, Day 18, Rep 2, K27ac, ActiveMotif |
| GSM6235112 |
GM21, Day 18, Rep 1, K4me1, ActiveMotif |
| GSM6235113 |
GM21, Day 18, Rep 2, K4me1, ActiveMotif |
| GSM6235114 |
GM21, Day 18, Rep 1, input |
| GSM6235115 |
GM21, Day 18, Rep 2, input |
| GSM6235116 |
GM21, Day 22, Rep 1, K27ac, ActiveMotif |
| GSM6235117 |
GM21, Day 22, Rep 2, K27ac, ActiveMotif |
| GSM6235118 |
GM21, Day 22, Rep 1, K4me1, ActiveMotif |
| GSM6235119 |
GM21, Day 22, Rep 2, K4me1, ActiveMotif |
| GSM6235120 |
GM21, Day 22, Rep 1, input |
| GSM6235121 |
GM21, Day 22, Rep 2, input |
| GSM6235122 |
GM21, Day 32, Rep 1, K27ac, ActiveMotif |
| GSM6235123 |
GM21, Day 32, Rep 2, K27ac, ActiveMotif |
| GSM6235124 |
GM21, Day 32, Rep 1, K4me1, ActiveMotif |
| GSM6235125 |
GM21, Day 32, Rep 2, K4me1, ActiveMotif |
| GSM6235126 |
GM21, Day 32, Rep 1, input |
| GSM6235127 |
GM21, Day 32, Rep 2, input |
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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 |
PRJNA848201 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE205898_RAW.tar |
8.4 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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