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Title: Environmentally sensitive hotspots in the methylome of the early human embryo
Author: Silver, Matt J.
Saffari, Ayden
Kessler, Noah J.
Chandak, Gririraj R.
Fall, Caroline H. D.
Issarapu, Prachand
Dedaniya, Akshay
Betts, Modupeh
Moore, Sophie E.
Routledge, Michael N.
Herceg, Zdenko
Cuenin, Cyrille
Derakhshan, Maria
James, Philip T.
Monk, David
Prentice, Andrew M.
Keywords: Metilació
Issue Date: 6-Jan-2022
Publisher: eLife Sciences Publications, Ltd
Abstract: In humans, DNA methylation marks inherited from gametes are largely erased following fertilisation, prior to construction of the embryonic methylome. Exploiting a natural experiment of seasonal variation including changes in diet and nutritional status in rural Gambia, we analysed three datasets covering two independent child cohorts and identified 259 CpGs showing consistent associations between season of conception (SoC) and DNA methylation. SoC effects were most apparent in early infancy, with evidence of attenuation by mid-childhood. SoC-associated CpGs were enriched for metastable epialleles, parent-of-origin-specific methylation and germline differentially methylated regions, supporting a periconceptional environmental influence. Many SoC-associated CpGs overlapped enhancers or sites of active transcription in H1 embryonic stem cells and fetal tissues. Half were influenced but not determined by measured genetic variants that were independent of SoC. Environmental 'hotspots' providing a record of environmental influence at periconception constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease.
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It is part of: eLife, 2022
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ISSN: 2050-084X
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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