Ontology highlight
ABSTRACT:
PROVIDER: PRJNA685322 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13420000_1.fastq.gz | Fastqsanger.gz | |||
| SRR13420000_2.fastq.gz | Fastqsanger.gz | |||
| SRR13420001_1.fastq.gz | Fastqsanger.gz | |||
| SRR13420001_2.fastq.gz | Fastqsanger.gz | |||
| SRR13420002.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Genomic instability is an early event driving chromatin organization and “escape” from oncogene-induced senescence
| PRJNA685841 | ENA
Project description:Oncogene-induced senescence (OIS) is an inherent and important tumor suppressor mechanism. However, if not timely removed via immune surveillance, senescent cells will also present a detrimental side. Although this has mostly been attributed to the senescence-associated-secretory-phenotype (SASP) of these cells, we recently suggested that “escape” from the senescent state represents another unfavorable outcome. Here, we exploit genomic and functional data from a prototypical human epithelial cell model carrying an inducible CDC6 oncogene to identify an early-acquired recurrent chromosomal inversion, which harbors a locus encoding the circadian transcription factor BHLHE40. This inversion alone suffices for activation of BHLHE40 upon CDC6 induction and for driving cell cycle re-entry and malignant transformation. In summary, we provide strong evidence in support of genomic instability underlying “escape” from oncogene-induced senescence.
2021-03-31 | GSE163371 | GEO
Project description:Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence imposes a limit on proliferative potential that all cancer cells must bypass. Compared to proliferating cells, senescent cells exhibit marked chromatin re-organization. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread alterations in their DNA methylome. These changes are linked to mislocalization of the maintenance DNA methyltransferase (DNMT1) in cells approaching senescence, altered replication-coupled DNA methylation and de-repression of repetitive satellite sequences. Deficiency of DNMT1 triggers chromatin changes characteristic of senescence and expression of satellite sequences. Most importantly, but paradoxically, gains and losses of methylation in replicative senescence are similar to those in cancer, and this M-bM-^@M-^XreprogrammedM-bM-^@M-^Y methylation landscape is largely retained when cells escape or bypass senescence. In sum, altered regulation of DNMT1 in cells approaching replicative senescence contributes to changes in chromatin structure and function. Consequently, if senescent cells escape the proliferative barrier, they already harbor epigenetic changes likely to promote malignancy. Examination of methylation status in IMR90 cells
2013-11-25 | E-GEOD-48580 | biostudies-arrayexpress
Project description:SETD1A, a member of the Set1/COMPASS family maintaining H3K4 methylation in the promoters of transcriptionally active genes, is critical for the execution of developmental gene expression and is overexpressed in multiple cancers including breast cancer1-3. Here we show that SETD1A is essential for supporting cellular mitotic processes and consequentially, its depletion leads to senescence. SETD1A directly regulates the expression of several genes orchestrating mitosis and DNA damage responses and its depletion results in multiple mitotic defects including chromosome misalignment and segregation defects. Senescence-associated cell cycle arrest in SETD1A knockdown cells is independent of the mutational status of p53, RB and p16, key mediators of this process, instead, is sustained through direct transcriptional suppression of SKP2, the ubiquitin ligase, which degrades p27 and p21. Rare cells escape senescence and re-enter the cell cycle by restoring SKP2 expression but with enhanced genomic instability. In >200 cancer cell lines and in primary circulating tumor cells, expression of SETD1A correlates with genes involved in mitosis and cell cycle suggesting a role in suppressing senescence induced by aberrant mitosis. Thus, SETD1A encodes a chromatin modifier, whose modulation may maintain the balance between senescence and genomic instability in cells.
2019-07-08 | GSE117427 | GEO
Project description: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.
2023-04-05 | GSE206493 | GEO
Project description: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.
2023-04-05 | GSE206402 | GEO
Project description: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.
2023-04-05 | GSE205898 | GEO
Project description: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.
2023-04-05 | GSE205692 | GEO
Project description:Activation of oncogene signaling in primary cells generally results in cellular senescence. This process is not only considered to be tumor-protective, but also irreversible. However, if senescence induction can be circumvented, e.g. by additional genetic or epigenetic changes, tumor progression occurs. An in-vivo example for oncogene-induced senescence are human nevus cells, most of which bear oncogenic mutations in RAS/RAF/MAPK pathway genes. Here, we show that expression of the human melanoma oncogene N-RAS61K in cultured pigment cells initially induces OIS characterized by a highly multinucleated phenotype. Surprisingly, after prolonged periods of oncogene expression, mononucleated cells emerge from the multinucleated cells. They are highly proliferative, anoikis-resistent and induce fast growing and metastatic melanoma upon transplantation into nude mice. During long-term oncogene expression and the corresponding development of anoikis iresistance, expression of melanocyte-specific genes is lost. Our data demonstrate that the induction of oncogene-induced senescence is not just a failsafe escape mechanism, but also provides a source for highly aggressive tumor cells. total samples analysed are 4
2014-01-20 | E-GEOD-27010 | biostudies-arrayexpress