Environmentally sensitive hotspots in the methylome of the early human embryo

Matt J Silver, Ayden Saffari, Noah J Kessler, Giriraj R Chandak, Caroline HD Fall, Prachand Issarapu, Akshay Dedaniya, Modupeh Betts, Sophie E Moore, Philip T James, David Monk, Andrew M Prentice

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Received Date: 3rd April 20

In humans, DNA methylation marks inherited from sperm and egg are largely erased immediately following conception, prior to construction of the embryonic methylome. Exploiting a natural experiment of cyclical seasonal variation including changes in diet and nutritional status in rural Gambia, we replicated 125 loci with a common season-of-conception methylation signature in two independent child cohorts, providing evidence of environmental effects on DNA methylation in the early embryo that persist at least until mid-childhood. Bioinformatic analysis revealed that these loci were highly enriched for metastable epialleles, parent-of-origin specific methylation and regions hypomethylated in sperm, and for H3K9me3 and H3K27me3 histone marks in multiple tissues. They tended to co-locate with endogenous retroviral (ERV1, ERVK) elements. Identified loci were influenced but not determined by measured genetic variation, notably through gene-environment interactions. To the extent that early methylation changes impact gene expression, environmental sensitivity during early embryo genomic remethylation could thus constitute a sense-record-adapt mechanism linking early environment to later phenotype.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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