Establishment of environmentally sensitive DNA methylation states in the very early human embryo - Supplementary Materials

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Kessler, NJ, Waterland, RA, Prentice, AM and Silver, MJ. 2018. Establishment of environmentally sensitive DNA methylation states in the very early human embryo - Supplementary Materials. [Online]. Science Advances. Available from: - http://advances.sciencemag.org/content/suppl/2018/07/09/4.7.eaat2624.DC1

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The molecular mechanisms responsible for the developmental origins of later disease are currently unknown. We previously demonstrated that women’s periconceptional nutrition predicts their offspring’s DNA methylation at metastable epialleles (MEs). We present a genome-wide screen yielding 687 MEs and track their trajectories across nine developmental stages in human in vitro fertilization embryos. MEs exhibit highly unusual methylation dynamics across the implantation-gastrulation transition, producing a large excess of intermediate methylation states, suggesting the potential for differential programming in response to external signals. Using a natural experiment in rural Gambia, we show that genomic regions sensitive to season of conception are highly enriched for MEs and show similar atypical methylation patterns. MEs are enriched for proximal enhancers and transcription start sites and are influenced by genotype. Together, these observations position MEs as distinctive epigenomic features programmed in the early embryo, sensitive to genetic and periconceptional environment, and with the potential to influence phenotype.

Published in a 3rd party system Date: 11 July 2018
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Data Creators(s): Kessler, NJ, Waterland, RA, Prentice, AM and Silver, MJ
LSHTM Faculty/Department: Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
Participating Institutions: London School of Hygiene & Tropical Medicine, London, United Kingdom, Baylor College of Medicine, Houston, Texas, United States of America

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