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Series GSE197512 Query DataSets for GSE197512
Status Public on Jul 25, 2022
Title Cell division drives DNA methylation loss in late-replicating domains in primary human cells [methylation array]
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary We present the first experimental evidence that loss of DNA methylation at late-replicating regions, widely documented in aging and cancer, is directly driven by cell division. DNA hypomethylation, particularly at low-density CpGs in A:T-rich, partially methylated domains (PMD solo-WCGWs), tracks cumulative population doublings in primary cell culture. Cell cycle deceleration or full arrest resulted in a proportional decrease in the rate of DNA methylation loss. Lower culture oxygen conditions resulted in a slowed rate of methylation loss, suggesting that these CpGs may also be vulnerable to methylation loss during unscheduled, repair-associated methylation maintenance as well as scheduled, replication-associated methylation maintenance. By studying this methylation context in immortalized primary cells, we identified genomic and epigenomic features that are resistant or more susceptible to methylation loss. Finally, we leveraged this extensive DNA methylation dataset to develop a refined metric for the relative cumulative mitotic histories of human cells. These RNA-sequencing data accompany the larger DNA methylation dataset.
 
Overall design DNA methylation in serially passaged primary human cell lines was profiled via human methylationEPIC array. Multiple sub-experiments are included: primary cells were either cultured under standard conditions, under low oxygen, with growth arresting agent mitomycin C, with differential serum concentrations , or after lentiviral transduction with TERT expression vector. Controls are included within each sub-experiment.
 
Contributor(s) Endicott JL, Laird PW, Shen H, Nolte PA
Citation(s) 36347867
Submission date Feb 26, 2022
Last update date Nov 30, 2022
Contact name Peter W Laird
E-mail(s) Peter.Laird@vai.org
Organization name Van Andel Institute
Department Epigenetics
Lab Peter W Laird
Street address 333 Bostwick Ave NE
City Grand Rapids
State/province MI
ZIP/Postal code 49503
Country USA
 
Platforms (1)
GPL23976 Illumina Infinium HumanMethylation850 BeadChip
Samples (372)
GSM5918847 FSF1_1
GSM5918848 FSF1_2
GSM5918849 FSF1_3
This SubSeries is part of SuperSeries:
GSE197545 Cell division drives DNA methylation loss in late-replicating domains in primary human cells
Relations
BioProject PRJNA810865

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE197512_RAW.tar 5.1 Gb (http)(custom) TAR (of IDAT)
Raw data provided as supplementary file
Processed data included within Sample table

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