Environmentally sensitive hotspots in the methylome of the early human embryo.

Autor: Silver MJ; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Gambia, United Kingdom., Saffari A; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Gambia, United Kingdom., Kessler NJ; Department of Genetics, University of Cambridge, Cambridge, United Kingdom., Chandak GR; Genomic Research on Complex Diseases, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Fall CHD; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom., Issarapu P; Genomic Research on Complex Diseases, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Dedaniya A; Genomic Research on Complex Diseases, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Betts M; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Gambia, United Kingdom., Moore SE; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Gambia, United Kingdom.; Department of Women and Children's Health, King's College London, London, United Kingdom., Routledge MN; School of Medicine, University of Leeds, Leeds, United Kingdom.; School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China., Herceg Z; Epigenomics and Mechanisms Branch, International Agency For Research On Cancer, Lyon, France., Cuenin C; Epigenomics and Mechanisms Branch, International Agency For Research On Cancer, Lyon, France., Derakhshan M; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Gambia, United Kingdom., James PT; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Gambia, United Kingdom., Monk D; Biomedical Research Centre, University of East Anglia, Norwich, United Kingdom.; Bellvitge Institute for Biomedical Research, Barcelona, Spain., Prentice AM; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Gambia, United Kingdom.
Jazyk: angličtina
Zdroj: ELife [Elife] 2022 Feb 21; Vol. 11. Date of Electronic Publication: 2022 Feb 21.
DOI: 10.7554/eLife.72031
Abstrakt: 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.
Competing Interests: MS, AS, NK, GC, CF, PI, AD, MB, SM, MR, ZH, CC, MD, PJ, DM, AP No competing interests declared
(© 2022, Silver et al.)
Databáze: MEDLINE