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Generation of Human Alloantigen-specific T Cells from Peripheral Blood
Published on: November 21, 2014
Age-related DNA hydroxymethylation is enriched for gene expression and immune system processes in human peripheral
Nicholas D Johnson1,2, Luoxiu Huang1, Ronghua Li1
1Department of Human Genetics, Emory University, Atlanta, GA, USA.
Abstract:
DNA methylation (DNAm) has a well-established association with age in many tissues, including peripheral blood mononuclear cells (PBMCs). Compared to DNAm, the closely related epigenetic modification known as DNA hydroxymethylation (DNAhm) was much more recently discovered in mammals. Preliminary investigations have observed a positive correlation between gene body DNAhm and cis-gene expression. While some of these studies have observed an association between age and global DNAhm, none have investigated region-specific age-related DNAhm in human blood samples. In this study, we investigated DNAhm and gene expression in PBMCs of 10 young and 10 old, healthy female volunteers. Thousands of regions were differentially hydroxymethylated in the old vs. young individuals in gene bodies, exonic regions, enhancers, and promoters. Consistent with previous work, we observed directional consistency between age-related differences in DNAhm and gene expression. Further, age-related DNAhm and genes with high levels of DNAhm were enriched for immune system processes which may support a role of age-related DNAhm in immunosenescence.
Insights
Epigenetic changes in DNA hydroxymethylation (DNAhm) correlate with aging in human blood cells. Age-related DNAhm patterns are linked to gene expression and immune system function, suggesting a role in immunosenescence.
Area of Science:
- Epigenetics
- Genomics
- Immunology
Background:
- DNA methylation (DNAm) is linked to aging in various tissues.
- DNA hydroxymethylation (DNAhm) is a related epigenetic modification with emerging roles.
- Previous studies noted global DNAhm and age correlations, but region-specific analysis in blood was lacking.
Purpose of the Study:
- To investigate region-specific DNAhm and its relationship with gene expression in aging human peripheral blood mononuclear cells (PBMCs).
- To explore the role of age-related DNAhm in immune system processes.
Main Methods:
- Analysis of DNAhm and gene expression in PBMCs from young and old healthy female volunteers.
- Genome-wide investigation of differentially hydroxymethylated regions in gene bodies, exons, enhancers, and promoters.
Main Results:
- Thousands of regions showed differential DNAhm between young and old individuals.
- Age-related changes in DNAhm showed directional consistency with gene expression.
- Age-related DNAhm and genes with high DNAhm levels were enriched in immune system pathways.
Conclusions:
- Region-specific DNAhm is altered with age in human PBMCs.
- Age-related DNAhm patterns are associated with changes in gene expression and immune function.
- DNAhm may play a significant role in immunosenescence.
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