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dc.contributor.authorByun, Hyang-Min
dc.contributor.authorNordio, Francesco
dc.contributor.authorCoull, Brent Andrew
dc.contributor.authorTarantini, Letizia
dc.contributor.authorHou, Lifang
dc.contributor.authorBonzini, Matteo
dc.contributor.authorApostoli, Pietro
dc.contributor.authorBertazzi, Pier Alberto
dc.contributor.authorBaccarelli, Andrea
dc.date.accessioned2013-04-03T19:14:53Z
dc.date.issued2012
dc.identifier.citationByun, Hyang-Min, Francesco Nordio, Brent A. Coull, Letizia Tarantini, Lifang Hou, Matteo Bonzini, Pietro Apostoli, Pier Alberto Bertazzi, and Andrea Baccarelli. 2012. Temporal stability of epigenetic markers: sequence characteristics and predictors of short-term dna methylation variations. PLoS ONE 7(6): e39220.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10496408
dc.description.abstractBackground: DNA methylation is an epigenetic mechanism that has been increasingly investigated in observational human studies, particularly on blood leukocyte DNA. Characterizing the degree and determinants of DNA methylation stability can provide critical information for the design and conduction of human epigenetic studies. Methods We measured DNA methylation in 12 gene-promoter regions (APC, p16, p53, RASSF1A, CDH13, eNOS, ET-1, IFNγ, IL-6, TNFα, iNOS, and hTERT) and 2 of non-long terminal repeat elements, i.e., L1 and Alu in blood samples obtained from 63 healthy individuals at baseline (Day 1) and after three days (Day 4). DNA methylation was measured by bisulfite-PCR-Pyrosequencing. We calculated intraclass correlation coefficients (ICCs) to measure the within-individual stability of DNA methylation between Day 1 and 4, subtracted of pyrosequencing error and adjusted for multiple covariates. Results: Methylation markers showed different temporal behaviors ranging from high (IL-6, ICC = 0.89) to low stability (APC, ICC = 0.08) between Day 1 and 4. Multiple sequence and marker characteristics were associated with the degree of variation. Density of CpG dinucleotides nearby the sequence analyzed (measured as CpG(o/e) or G+C content within ±200bp) was positively associated with DNA methylation stability. The 3′ proximity to repeat elements and range of DNA methylation on Day 1 were also positively associated with methylation stability. An inverted U-shaped correlation was observed between mean DNA methylation on Day 1 and stability. Conclusions: The degree of short-term DNA methylation stability is marker-dependent and associated with sequence characteristics and methylation levels.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0039220en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3379987/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectGeneticsen_US
dc.subjectEpigeneticsen_US
dc.subjectDNA modificationen_US
dc.subjectGene Expressionen_US
dc.subjectPopulation Biologyen_US
dc.subjectEpidemiologyen_US
dc.subjectEnvironmental Epidemiologyen_US
dc.subjectGenetic Epidemiologyen_US
dc.subjectMedicineen_US
dc.subjectBiomarker Epidemiologyen_US
dc.subjectMolecular Epidemiologyen_US
dc.titleTemporal Stability of Epigenetic Markers: Sequence Characteristics and Predictors of Short-Term DNA Methylation Variationsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorCoull, Brent Andrew
dc.date.available2013-04-03T19:14:53Z
dc.identifier.doi10.1371/journal.pone.0039220*
dash.contributor.affiliatedByun, Hyang-Min
dash.contributor.affiliatedNordio, Francesco
dash.contributor.affiliatedBaccarelli, Andrea
dash.contributor.affiliatedCoull, Brent
dc.identifier.orcid0000-0002-3436-0640


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