Human non-CpG methylation patterns display both tissue-specific and inter-individual differences suggestive of underlying function
Human non-CpG methylation patterns display both tissue-specific and inter-individual differences suggestive of underlying function
DNA methylation (DNAm) in mammals is mostly examined within the context of CpG dinucleotides. Non-CpG DNAm is also widespread across the human genome, but the functional relevance, tissue-specific disposition, and inter-individual variability has not been widely studied. Our aim was to examine non-CpG DNAm in the wider methylome across multiple tissues from the same individuals to better understand non-CpG DNAm distribution within different tissues and individuals and in relation to known genomic regulatory features. DNA methylation in umbilical cord and cord blood at birth, and peripheral venous blood at age 12–13 y from 20 individuals from the Southampton Women’s Survey cohort was assessed by Agilent SureSelect methyl-seq. Hierarchical cluster analysis (HCA) was performed on CpG and non-CpG sites and stratified by specific cytosine environment. Analysis of tissue and inter-individual variation was then conducted in a second dataset of 12 samples: eight muscle tissues, and four aliquots of cord blood pooled from two individuals. HCA using methylated non-CpG sites showed different clustering patterns specific to the three base-pair triplicate (CNN) sequence. Analysis of CAC sites with non-zero methylation showed that samples clustered first by tissue type, then by individual (as observed for CpG methylation), while analysis using non-zero methylation at CAT sites showed samples grouped predominantly by individual. These clustering patterns were validated in an independent dataset using cord blood and muscle tissue. This research suggests that CAC methylation can have tissue-specific patterns, and that individual effects, either genetic or unmeasured environmental factors, can influence CAT methylation.
CAC, CAT, CHG, CHH, CNN, CpG, DNA methylation, HCA, cluster, comparison, hierarchical clustering analysis, human, individual-specific, methylation, methylation patterns, muscle, non-CpG, peripheral blood, tissue-specific, umbilical cord, umbilical cord blood
Titcombe, Philip
a84c9fad-0580-42f9-8bb6-db0fe20435aa
Murray, Robert
c3e973b5-525c-49b3-96ee-af60a666a0f4
Hewitt, Matthew
0f587519-9c70-44d6-8cd6-3f7866375c5e
Antoun, Elie
10fc5678-b33c-4410-977d-b11234031791
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Inskip, Hazel
5fb4470a-9379-49b2-a533-9da8e61058b7
Holbrook, Joanna D
69989b79-2710-4f12-946e-c6214e1b6513
Godfrey, Keith
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Hanson, Mark
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Barton, Sheila
4f674382-ca0b-44ad-9670-e71a0b134ef0
30 August 2021
Titcombe, Philip
a84c9fad-0580-42f9-8bb6-db0fe20435aa
Murray, Robert
c3e973b5-525c-49b3-96ee-af60a666a0f4
Hewitt, Matthew
0f587519-9c70-44d6-8cd6-3f7866375c5e
Antoun, Elie
10fc5678-b33c-4410-977d-b11234031791
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Inskip, Hazel
5fb4470a-9379-49b2-a533-9da8e61058b7
Holbrook, Joanna D
69989b79-2710-4f12-946e-c6214e1b6513
Godfrey, Keith
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Hanson, Mark
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Barton, Sheila
4f674382-ca0b-44ad-9670-e71a0b134ef0
Titcombe, Philip, Murray, Robert, Hewitt, Matthew, Antoun, Elie, Cooper, Cyrus, Inskip, Hazel, Holbrook, Joanna D, Godfrey, Keith, Lillycrop, Karen, Hanson, Mark and Barton, Sheila
(2021)
Human non-CpG methylation patterns display both tissue-specific and inter-individual differences suggestive of underlying function.
Epigenetics.
(doi:10.1080/15592294.2021.1950990).
Abstract
DNA methylation (DNAm) in mammals is mostly examined within the context of CpG dinucleotides. Non-CpG DNAm is also widespread across the human genome, but the functional relevance, tissue-specific disposition, and inter-individual variability has not been widely studied. Our aim was to examine non-CpG DNAm in the wider methylome across multiple tissues from the same individuals to better understand non-CpG DNAm distribution within different tissues and individuals and in relation to known genomic regulatory features. DNA methylation in umbilical cord and cord blood at birth, and peripheral venous blood at age 12–13 y from 20 individuals from the Southampton Women’s Survey cohort was assessed by Agilent SureSelect methyl-seq. Hierarchical cluster analysis (HCA) was performed on CpG and non-CpG sites and stratified by specific cytosine environment. Analysis of tissue and inter-individual variation was then conducted in a second dataset of 12 samples: eight muscle tissues, and four aliquots of cord blood pooled from two individuals. HCA using methylated non-CpG sites showed different clustering patterns specific to the three base-pair triplicate (CNN) sequence. Analysis of CAC sites with non-zero methylation showed that samples clustered first by tissue type, then by individual (as observed for CpG methylation), while analysis using non-zero methylation at CAT sites showed samples grouped predominantly by individual. These clustering patterns were validated in an independent dataset using cord blood and muscle tissue. This research suggests that CAC methylation can have tissue-specific patterns, and that individual effects, either genetic or unmeasured environmental factors, can influence CAT methylation.
Text
KEPI-2021-0060_R1 (00000002)
- Accepted Manuscript
Text
Supplementary tables and figures_revised_with_descriptions
Restricted to Repository staff only
Request a copy
More information
Accepted/In Press date: 29 June 2021
e-pub ahead of print date: 30 August 2021
Published date: 30 August 2021
Additional Information:
Funding Information:
KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. PT, RM, MHewitt, EA, CC, KMG, KAL, MHanson, SJB are part of academic research programmes that have received research funding from Abbott Nutrition, Nestec and Danone.
Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Keywords:
CAC, CAT, CHG, CHH, CNN, CpG, DNA methylation, HCA, cluster, comparison, hierarchical clustering analysis, human, individual-specific, methylation, methylation patterns, muscle, non-CpG, peripheral blood, tissue-specific, umbilical cord, umbilical cord blood
Identifiers
Local EPrints ID: 450168
URI: http://eprints.soton.ac.uk/id/eprint/450168
ISSN: 1559-2294
PURE UUID: 050f4c65-4647-434e-ae49-0b45d5662b59
Catalogue record
Date deposited: 14 Jul 2021 16:45
Last modified: 18 Mar 2024 05:05
Export record
Altmetrics
Contributors
Author:
Philip Titcombe
Author:
Robert Murray
Author:
Matthew Hewitt
Author:
Elie Antoun
Author:
Joanna D Holbrook
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics