Browsing by Author "Ding, Jingzhong"
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- Age-related variations in the methylome associated with gene expression in human monocytes and T cellsReynolds, Lindsay M.; Taylor, Jackson R.; Ding, Jingzhong; Lohman, Kurt; Johnson, Craig; Siscovick, David; Burke, Gregory L.; Post, Wendy; Shea, Steven; Jacobs, David R. Jr.; Stunnenberg, Hendrik G.; Kritchevsky, Stephen B.; Hoeschele, Ina; McCall, Charles E.; Herrington, David M.; Tracy, Russell P.; Liu, Yongmei (Springer Nature, 2014-11)Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age-and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process.
- Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosisLiu, Yongmei; Reynolds, Lindsay M.; Ding, Jingzhong; Hou, Li; Lohman, Kurt; Young, Tracey; Cui, Wei; Huang, Zhiqing; Grenier, Carole; Wan, Ma; Stunnenberg, Hendrik G.; Siscovick, David; Hou, Lifang; Psaty, Bruce M.; Rich, Stephen S.; Rotter, Jerome I.; Kaufman, Joel D.; Burke, Gregory L.; Murphy, Susan F.; Jacobs, David R. Jr.; Post, Wendy; Hoeschele, Ina; Bell, Douglas A.; Herrington, David M.; Parks, John S.; Tracy, Russell P.; McCall, Charles E.; Stein, James H. (Springer Nature, 2017-08-30)Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.
- Role of DNA methylation on the association between physical activity and cardiovascular diseases: results from the longitudinal multi-ethnic study of atherosclerosis (MESA) cohortShi, Hangchuan; Ossip, Deborah J.; Mayo, Nicole L.; Lopez, Daniel A.; Block, Robert C.; Post, Wendy S.; Bertoni, Alain G.; Ding, Jingzhong; Chen, Si; Yan, Chen; Xie, Zidian; Hoeschele, Ina; Liu, Yongmei; Li, Dongmei (2021-11-03)Background The complexity of physical activity (PA) and DNA methylation interaction in the development of cardiovascular disease (CVD) is rarely simultaneously investigated in one study. We examined the role of DNA methylation on the association between PA and CVD. Results The Multi-Ethnic Study of Atherosclerosis (MESA) cohort Exam 5 data with 1065 participants free of CVD were used for final analysis. The quartile categorical total PA variable was created by activity intensity (METs/week). During a median follow-up of 4.0 years, 69 participants developed CVD. Illumina HumanMethylation450 BeadChip was used to provide genome-wide DNA methylation profiles in purified human monocytes (CD14+). We identified 23 candidate DNA methylation loci to be associated with both PA and CVD. We used the structural equation modeling (SEM) approach to test the complex relationships among multiple variables and the roles of mediators. Three of the 23 identified loci (corresponding to genes VPS13D, PIK3CD and VPS45) remained as significant mediators in the final SEM model along with other covariates. Bridged by the three genes, the 2nd PA quartile (β = − 0.959; 95%CI: − 1.554 to − 0.449) and the 3rd PA quartile (β = − 0.944; 95%CI: − 1.628 to − 0.413) showed the greatest inverse associations with CVD development, while the 4th PA quartile had a relatively weaker inverse association (β = − 0.355; 95%CI: − 0.713 to − 0.124). Conclusions The current study is among the first to simultaneously examine the relationships among PA, DNA methylation, and CVD in a large cohort with long-term exposure. We identified three DNA methylation loci bridged the association between PA and CVD. The function of the identified genes warrants further investigation in the pathogenesis of CVD.