Document Detail

Factors underlying variable DNA methylation in a human community cohort.
MedLine Citation:
PMID:  23045638     Owner:  NLM     Status:  MEDLINE    
Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression. We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated.
Lucia L Lam; Eldon Emberly; Hunter B Fraser; Sarah M Neumann; Edith Chen; Gregory E Miller; Michael S Kobor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109 Suppl 2     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-17     Completed Date:  2013-01-16     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17253-60     Citation Subset:  IM    
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
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MeSH Terms
Cohort Studies
DNA Methylation / genetics*
Epigenesis, Genetic
Gene Expression
Genetics, Population
Leukocytes / metabolism
Life Change Events
Middle Aged
Principal Component Analysis
Promoter Regions, Genetic
Social Class
Stress, Psychological
Young Adult
Grant Support
Comment In:
Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):E1246   [PMID:  23493547 ]
Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):E1247   [PMID:  23667927 ]

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