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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 25, 2013 |
| Title |
Genome-wide methylation maps for Proliferating and Senescent cells |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
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 ‘reprogrammed’ 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.
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| Overall design |
Examination of methylation status in IMR90 cells
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| Contributor(s) |
Cruickshanks HA, McBryan T, Adams PD |
| Citation(s) |
24270890, 27457071 |
| Submission date |
Jul 08, 2013 |
| Last update date |
Apr 02, 2020 |
| Contact name |
Peter D. Adams |
| Organization name |
University of Glasgow, Beatson Institute for Cancer Research
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| Street address |
Switchback Rd, Bearsden
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| City |
Glasgow |
| ZIP/Postal code |
G61 1BD |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA210744 |
| SRA |
SRP026604 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48580_Proliferating.vs.SV40.Bypass.PooledG.DMR.down.bed.gz |
325.6 Kb |
(ftp)(http) |
BED |
| GSE48580_Proliferating.vs.SV40.Bypass.PooledG.DMR.up.bed.gz |
125.6 Kb |
(ftp)(http) |
BED |
| GSE48580_Proliferating.vs.Senescent.PooledG.DMR.down.bed.gz |
303.4 Kb |
(ftp)(http) |
BED |
| GSE48580_Proliferating.vs.Senescent.PooledG.DMR.up.bed.gz |
240.4 Kb |
(ftp)(http) |
BED |
| GSE48580_RAW.tar |
3.0 Gb |
(http)(custom) |
TAR (of BIGWIG, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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