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Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo.

Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo.
Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo.

We analysed DNA methylation data from 30 datasets comprising 3474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4143 hypervariable CpGs ('hvCpGs') with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by genetic variation, and was not linked to probe reliability, epigenetic drift, age, sex or cell heterogeneity effects. hvCpG methylation tended to covary across tissues derived from different germ-layers and hvCpGs were enriched for proximity to ERV1 and ERVK retrovirus elements. hvCpGs were also enriched for loci previously associated with periconceptional environment, parent-of-origin-specific methylation, and distinctive methylation signatures in monozygotic twins. Together, these properties position hvCpGs as strong candidates for studying how stochastic and/or environmentally influenced DNA methylation states which are established in the early embryo and maintained stably thereafter can influence life-long health and disease.

0305-1048
6735-6752
Derakhshan, Maria
cda18314-cc31-4397-a2c4-f4258ab24f09
Kessler, Noah J.
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Miho, Ishida
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Demetriou, Charalambos
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Brucato, Nicolas
871a62ec-a2ea-41f0-90a8-730dc8071852
Moore, Gudrun E.
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Fall, Caroline
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Chandak, Giriraj R.
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Ricaut, Francois-Xavier
55343d3f-be95-4146-b904-a68b1643139e
Prentice, Andrew M.
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Hellenthal, Garrett
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Silver, Matt J.
a704b241-b538-460a-b526-28a6e81a1915
Derakhshan, Maria
cda18314-cc31-4397-a2c4-f4258ab24f09
Kessler, Noah J.
2442ea07-46ad-42cd-985b-333d2d917b89
Miho, Ishida
66934201-a53a-4afb-a97c-bf3bb869ccc6
Demetriou, Charalambos
4e227e4a-4494-4489-8fd0-831734d85d0f
Brucato, Nicolas
871a62ec-a2ea-41f0-90a8-730dc8071852
Moore, Gudrun E.
b94d7cf8-eec7-40b0-b256-11947cbb3f0b
Fall, Caroline
7171a105-34f5-4131-89d7-1aa639893b18
Chandak, Giriraj R.
d9d4d4ba-6a4b-450d-8889-02e599ca0e1c
Ricaut, Francois-Xavier
55343d3f-be95-4146-b904-a68b1643139e
Prentice, Andrew M.
6b851f61-f989-48f6-8109-9a7408254728
Hellenthal, Garrett
6ed6f502-2192-4303-a5fc-07679e15953b
Silver, Matt J.
a704b241-b538-460a-b526-28a6e81a1915

Derakhshan, Maria, Kessler, Noah J., Miho, Ishida, Demetriou, Charalambos, Brucato, Nicolas, Moore, Gudrun E., Fall, Caroline, Chandak, Giriraj R., Ricaut, Francois-Xavier, Prentice, Andrew M., Hellenthal, Garrett and Silver, Matt J. (2022) Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo. Nucleic Acids Research, 50 (12), 6735-6752. (doi:10.1093/nar/gkac503).

Record type: Article

Abstract

We analysed DNA methylation data from 30 datasets comprising 3474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4143 hypervariable CpGs ('hvCpGs') with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by genetic variation, and was not linked to probe reliability, epigenetic drift, age, sex or cell heterogeneity effects. hvCpG methylation tended to covary across tissues derived from different germ-layers and hvCpGs were enriched for proximity to ERV1 and ERVK retrovirus elements. hvCpGs were also enriched for loci previously associated with periconceptional environment, parent-of-origin-specific methylation, and distinctive methylation signatures in monozygotic twins. Together, these properties position hvCpGs as strong candidates for studying how stochastic and/or environmentally influenced DNA methylation states which are established in the early embryo and maintained stably thereafter can influence life-long health and disease.

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Accepted/In Press date: 27 May 2022
Published date: 8 July 2022
Additional Information: Publisher Copyright: © 2022 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.

Identifiers

Local EPrints ID: 468765
URI: http://eprints.soton.ac.uk/id/eprint/468765
ISSN: 0305-1048
PURE UUID: dc9e766e-094e-40e0-8274-bb79856c6172
ORCID for Caroline Fall: ORCID iD orcid.org/0000-0003-4402-5552

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Date deposited: 25 Aug 2022 16:35
Last modified: 15 Nov 2022 02:32

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Contributors

Author: Maria Derakhshan
Author: Noah J. Kessler
Author: Ishida Miho
Author: Charalambos Demetriou
Author: Nicolas Brucato
Author: Gudrun E. Moore
Author: Caroline Fall ORCID iD
Author: Giriraj R. Chandak
Author: Francois-Xavier Ricaut
Author: Andrew M. Prentice
Author: Garrett Hellenthal
Author: Matt J. Silver

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