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Environmentally sensitive hotspots in the methylome of the early human embryo

Environmentally sensitive hotspots in the methylome of the early human embryo
Environmentally sensitive hotspots in the methylome of the early human embryo
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.
DNA methylation, Human, conception, early embryo, metastable epiallele, nutrition, parent-of-origin effects
2050-084X
e72031
Silver, Matt J.
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Saffari, Ayden
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Kessler, Noah J.
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Chandak, Giriraj R.
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Fall, Caroline
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Issarapu, Prachand
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Dedaniya, Akshay
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Betts, Modupeh
78d7f425-c9f6-4daf-a435-a589ac014155
Moore, Sophie E.
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Routledge, Michael N
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Herceg, Zdenko
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Cuenin, Cyrille
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Derakhshan, Maria
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James, Philip T.
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Monk, David
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Prentice, Andrew M.
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Silver, Matt J.
a704b241-b538-460a-b526-28a6e81a1915
Saffari, Ayden
586ef334-e08f-4ca0-b2f6-575a453d5fa3
Kessler, Noah J.
2442ea07-46ad-42cd-985b-333d2d917b89
Chandak, Giriraj R.
d9d4d4ba-6a4b-450d-8889-02e599ca0e1c
Fall, Caroline
7171a105-34f5-4131-89d7-1aa639893b18
Issarapu, Prachand
f980880e-53a1-477d-affc-7a2f7328504b
Dedaniya, Akshay
02a2cbdf-c16b-47c4-a254-f1c24dd2e6ea
Betts, Modupeh
78d7f425-c9f6-4daf-a435-a589ac014155
Moore, Sophie E.
bea65f65-3f11-45cd-96d2-c088a18ccc55
Routledge, Michael N
ff1a548d-466e-4949-afb6-1b658122e63f
Herceg, Zdenko
489f5d2b-bf53-4ddd-89fc-68ec41b5d528
Cuenin, Cyrille
65c4c33c-745c-44e3-8660-92959931f7f8
Derakhshan, Maria
cda18314-cc31-4397-a2c4-f4258ab24f09
James, Philip T.
07c09e26-1d23-4dca-b3f4-e322b33bf72f
Monk, David
3afd0958-2e57-4135-a20a-462f59dce4d5
Prentice, Andrew M.
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Silver, Matt J., Saffari, Ayden, Kessler, Noah J., Chandak, Giriraj R., Fall, Caroline, Issarapu, Prachand, Dedaniya, Akshay, Betts, Modupeh, Moore, Sophie E., Routledge, Michael N, Herceg, Zdenko, Cuenin, Cyrille, Derakhshan, Maria, James, Philip T., Monk, David and Prentice, Andrew M. (2022) Environmentally sensitive hotspots in the methylome of the early human embryo. eLife, e72031, [11]. (doi:10.7554/eLife.72031.sa0).

Record type: Article

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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More information

Accepted/In Press date: 18 February 2022
e-pub ahead of print date: 21 February 2022
Published date: 21 February 2022
Keywords: DNA methylation, Human, conception, early embryo, metastable epiallele, nutrition, parent-of-origin effects

Identifiers

Local EPrints ID: 455996
URI: http://eprints.soton.ac.uk/id/eprint/455996
ISSN: 2050-084X
PURE UUID: 8c03f52a-d3e7-4a6b-ad5f-5635a23034e7
ORCID for Caroline Fall: ORCID iD orcid.org/0000-0003-4402-5552

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Date deposited: 12 Apr 2022 16:30
Last modified: 17 Mar 2024 02:36

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Contributors

Author: Matt J. Silver
Author: Ayden Saffari
Author: Noah J. Kessler
Author: Giriraj R. Chandak
Author: Caroline Fall ORCID iD
Author: Prachand Issarapu
Author: Akshay Dedaniya
Author: Modupeh Betts
Author: Sophie E. Moore
Author: Michael N Routledge
Author: Zdenko Herceg
Author: Cyrille Cuenin
Author: Maria Derakhshan
Author: Philip T. James
Author: David Monk
Author: Andrew M. Prentice

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