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Series GSE48580 Query DataSets for GSE48580
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
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.
Overall design Examination of methylation status in IMR90 cells
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
Street address Switchback Rd, Bearsden
City Glasgow
ZIP/Postal code G61 1BD
Country United Kingdom
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (9)
GSM1181642 Proliferating BS-seq Rep1
GSM1181646 Proliferating BS-seq Rep2
GSM1181647 Proliferating BS-seq Rep3
BioProject PRJNA210744
SRA SRP026604

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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)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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