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Differential DNA Methylation between Obese and Normal Weight Women in CD4+ and CD8+ T cells, and CD16+ neutrophils
Author(s) -
Hohos Natalie M,
Smith Alicia K,
Kilaru Varun,
Park Hea Jin,
Hausman Dorothy B,
Bailey Lynn B,
Lewis Richard D,
Meagher Richard B
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.431.1
Subject(s) - dna methylation , methylation , cd8 , epigenetics , biology , microbiology and biotechnology , cd16 , epigenome , cytosine , dna , adipose tissue , bisulfite sequencing , methylated dna immunoprecipitation , immunology , endocrinology , gene , biochemistry , immune system , gene expression , cd3
Diet, nutrition, and perhaps other lifestyle factors are proposed to alter chromatin structures such as DNA cytosine modification and epigenome‐regulated gene expression. Most dietary and nutritional studies to date analyze DNA cytosine methylation differences in mixed cell populations (i.e. PBMC's or whole blood); however each leukocyte cell type has a distinct DNA cytosine methylation profile. When multiple white cell types are examined together, the methylation data reflect a weight average of all cell types and the biologically meaningful results for each individual cell type are often lost. In order to explore more statistically and biologically significant DNA cytosine methylation data associated with obesity, we examined DNA methylation profiles in three distinct cell types isolated from peripheral blood. CD4+ T cells, CD8+ T cells and CD16+ neutrophils were reiteratively isolated from blood samples in normal weight (BMI 18.5–24.9 kg/m 2 ) and obese (BMI >30 kg/m 2 ) women (18–35 y). DNA 5′‐methylcytosine (5mC) levels were measured across > 485,000 CG sites using the HumanMethylation450 BeadChip (Illumina © ) for each of the three cell types. After controlling the false discovery rate (q‐value < 0.05), 19 CG sites were differentially methylated between the obese and normal weight women in CD4+ T cells, 16 CG sites in CD8+ T cells and 0 CG sites in CD16+ neutrophils. None of the differentially methylated CG sites overlapped between the CD4+ and CD8+ cells. The amount of visceral adipose tissue (VAT) was found to be associated with the level of methylation in 79 CG sites (q‐value < 0.05) in CD4+ T cells while no differences were found in either of the other cell types. Associations of 5mCs with obesity and VAT ranged from 10 −5 < p < 10 −9 . It appears that the methylome of these three cell types each respond quite differently to obesity and the levels of VAT, illustrating the importance of examining epigenetic marks in single cell types. Among the differentially methylated CGs in CD4+ and CD8+ T cells were sites in genes potentially involved in lipid metabolism ( LIAS, ACSM6, AGPAT1, ALDH3B1 ), metabolic syndrome (SLC2A1/GLUT1, CASZ1, HOXB5, LIAS , LRP1, WNT5B, IGFBP4, RPH3AL, SCARF1), chromatin remodeling (BRD4, SAP30, FANCC, JARID2, PRDM11) , Alzheimer's disease (CLSTN1, LRP1) , progenitor cell development ( FADD, JARID2, LGR5) and the cell cycle (BRD4, MYO10, CDC20B, MAD1L1) . In summary, by examining DNA methylation differences in three cell types, we identified highly significant sites that were differentially methylated between the normal and obese weight women with biological relevance to obesity. Future work will continue to characterize response of the DNA methylome to nutrition and lifestyle choices in relation to obesity.