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Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo

Abstract : Abstract We analysed DNA methylation data from 30 datasets comprising 3474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4143 hypervariable CpGs (‘hvCpGs’) with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by genetic variation, and was not linked to probe reliability, epigenetic drift, age, sex or cell heterogeneity effects. hvCpG methylation tended to covary across tissues derived from different germ-layers and hvCpGs were enriched for proximity to ERV1 and ERVK retrovirus elements. hvCpGs were also enriched for loci previously associated with periconceptional environment, parent-of-origin-specific methylation, and distinctive methylation signatures in monozygotic twins. Together, these properties position hvCpGs as strong candidates for studying how stochastic and/or environmentally influenced DNA methylation states which are established in the early embryo and maintained stably thereafter can influence life-long health and disease.
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Submitted on : Thursday, August 25, 2022 - 1:12:00 PM
Last modification on : Tuesday, September 6, 2022 - 3:51:17 AM

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Maria Derakhshan, Noah Kessler, Miho Ishida, Charalambos Demetriou, Nicolas Brucato, et al.. Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo. Nucleic Acids Research, Oxford University Press, 2022, 50 (12), pp.6735-6752. ⟨10.1093/nar/gkac503⟩. ⟨hal-03753713⟩

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