DNA hydroxymethylation age of human blood determined by capillary hydrophilic-interaction liquid chromatography/mass spectrometry

Xiong, Jun; Jiang, Han-Peng; Peng, Chunyan; Deng, Qianyun; Lan, Meng-Dan; Zeng, Huan; Zheng, Fang; Feng, Yu‐Qi

doi:10.1186/s13148-015-0109-x

Cited by 29 publications

(19 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Supporting this idea, we found moderate enrichment of age-related DHMRs at CpG shores, CpG shelves, promoters, 5ʹUTRs, exons, introns, and 3ʹUTRs compared to a random distribution ( Figure S1B). While this enrichment of DHMRs at specific genomic locations was subtle, DHMRs also showed a clear bias toward hypo-hydroxymethylation with age (Table 1), a pattern supported by human studies showing decreased 5hmC levels in blood with age [21,22]. Combined, these data suggest that age-related changes in 5hmC are non-random, and that DNA hydroxymethylation could play a role in the aging process.…”

Section: Discussionmentioning

confidence: 56%

Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood

et al. 2018

View full text Add to dashboard Cite

DNA methylation at cytosine-phosphate-guanine (CpG) dinucleotides changes as a function of age in humans and animal models, a process that may contribute to chronic disease development. Recent studies have investigated the role of an oxidized form of DNA methylation - 5-hydroxymethylcytosine (5hmC) - in the epigenome, but its contribution to age-related DNA methylation remains unclear. We tested the hypothesis that 5hmC changes with age, but in a direction opposite to 5-methylcytosine (5mC), potentially playing a distinct role in aging. To characterize epigenetic aging, genome-wide 5mC and 5hmC were measured in longitudinal blood samples (2, 4, and 10 months of age) from isogenic mice using two sequencing methods - enhanced reduced representation bisulfite sequencing and hydroxymethylated DNA immunoprecipitation sequencing. Examining the epigenome by age, we identified 28,196 unique differentially methylated CpGs (DMCs) and 8,613 differentially hydroxymethylated regions (DHMRs). Mouse blood showed a general pattern of epigenome-wide hypermethylation and hypo-hydroxymethylation with age. Comparing age-related DMCs and DHMRs, 1,854 annotated genes showed both differential 5mC and 5hmC, including one gene - Nfic - at five CpGs in the same 250 bp chromosomal region. At this region, 5mC and 5hmC levels both decreased with age. Reflecting these age-related epigenetic changes, Nfic RNA expression in blood decreased with age, suggesting that age-related regulation of this gene may be driven by 5hmC, not canonical DNA methylation. Combined, our genome-wide results show age-related differential 5mC and 5hmC, as well as some evidence that changes in 5hmC may drive age-related DNA methylation and gene expression.

show abstract

Section: Discussionmentioning

confidence: 56%

Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Accumulated data supported the idea that DNA methylation showed reduced stringency in maintenance over the lifespan, resulting in an increase in inter-individual variability along with the overall decrease in DNA methylation [ 36 ]. Our previous study [ 37 ] also observed a slight negative correlation between 5-mC and chronological age.…”

Section: Discussionmentioning

confidence: 61%

“…The mass spectrometry detection was performed under positive electrospray ionization mode [ 37 ]. The target nucleosides were monitored by multiple reaction monitoring (MRM) mode using the mass transitions (precursor ions ➔ product ions) of dC (228.4 ➔ 112.2), T (243.3 ➔ 127.2), dA (252.4 ➔ 136.2), dG (268.4 ➔ 152.4), rC (244.4 ➔ 112.2), rU (245.4 ➔ 113.1), rA (268.4 ➔ 136.2), rG (284.5 ➔ 152.2), 5-mdC (242.3 ➔ 126.1), and 5-hmdC (258.2 ➔ 142.1).…”

Section: Methodsmentioning

confidence: 99%

Genomic 5-mC contents in peripheral blood leukocytes were independent protective factors for coronary artery disease with a specific profile in different leukocyte subtypes

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundAlterations in DNA methylation are demonstrated in atherosclerosis pathogenesis. However, changing rules of global DNA methylation and hydroxymethylation in peripheral blood leukocytes (PBLs) and different blood cell subtypes of coronary artery disease (CAD) patients are still inconclusive, and much less is known about mechanisms underlying.ResultsWe recruited 265 CAD patients and 270 healthy controls with genomic DNA from PBLs, of which 50 patients and 50 controls were randomly chosen with DNA from isolated neutrophils, lymphocytes and monocytes, and RNA from PBLs. Genomic 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) contents were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) assay. Genomic 5-mC contents were negatively associated with the serum total cholesterol (TC) level (P = 0.010), age (P = 0.016), and PBL classifications (P = 0.023), explaining 6.8% individual variation in controls. Furthermore, genomic 5-mC contents were inversely associated with an increased risk of CAD (odds ratio (OR) = 0.325, 95% confidence interval (CI) = 0.237~0.445, P = 2.62 × 10− 12), independent of PBL counts and classifications, age, sex, histories of hyperlipidemia, hypertension, and diabetes. Within-individual analysis showed a general 5-mC decrease in PBL subtypes, but significant difference was found in monocytes only (P = 0.001), accompanied by increased 5-hmC (P = 3.212 × 10− 4). In addition, coincident to the reduced DNMT1 expression in patients’ PBLs, the expression level of DNMT1 was significantly lower (P = 0.022) in oxidized low-density lipoprotein (ox-LDL) stimulated THP-1-derived foam cells compared to THP-1 monocytes, with decreased genomic 5-mdC content (P = 0.038).ConclusionsGlobal hypomethylation of blood cells defined dominantly by the monocyte DNA hypomethylation is independently associated with the risk of CAD in Chinese Han population. The importance of monocytes in atherosclerosis pathophysiology may demonstrate via an epigenetic pathway, but prospective studies are still needed to test the causality.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0443-x) contains supplementary material, which is available to authorized users.

show abstract

“… 40 , 41 Currently, global DNA hydroxymethylation is being characterised as a strong and reproducible trademark of chronological age, potentially acting on the assessment of health and disease prevention. 42 Truong et al 43 recently reported that the level of hydroxymethylation in peripheral blood T cells from humans is dependent on age, and is associated with a gradual decrease of TET3 expression levels during aging. However, in our study, we detected no influence of age on DNA global methylation and hydroxymethylation levels in skin tissue ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

Global and gene-specific DNA methylation and hydroxymethylation in human skin exposed and not exposed to sun radiation

Silva

Melo

Costa

et al. 2017

An. Bras. Dermatol.

View full text Add to dashboard Cite

Backgroundepigenomes can be influenced by environmental factors leading to the development of diseases.ObjectiveTo investigate the influence of sun exposure on global DNA methylation and hydroxymethylation status and at specific sites of the miR-9-1, miR-9-3 and MTHFR genes in skin samples of subjects with no history of skin diseases.MethodsSkin samples were obtained by punch on sun-exposed and sun-protected arm areas from 24 corpses of 16-89 years of age. Genomic DNA was extracted from skin samples that were ranked according to Fitzpatrick's criteria as light, moderate, and dark brown. Global DNA methylation and hydroxymethylation and DNA methylation analyses at specific sites were performed using ELISA and MSP, respectively.ResultsNo significant differences in global DNA methylation and hydroxymethylation levels were found among the skin areas, skin types, or age. However, gender-related differences were detected, where women showed higher methylation levels. Global DNA methylation levels were higher than hydroxymethylation levels, and the levels of these DNA modifications correlated in skin tissue. For specific sites, no differences among the areas were detected. Additional analyses showed no differences in the methylation status when age, gender, and skin type were considered; however, the methylation status of the miR-9-1 gene seems to be gender related.Study limitationsthere was no separation of dermis and epidermis and low sample size.Conclusionsun exposure does not induce changes in the DNA methylation and hydroxymethylation status or in miR-9-1, miR-9-3 and MTHFR genes for the studied skin types.

show abstract

DNA hydroxymethylation age of human blood determined by capillary hydrophilic-interaction liquid chromatography/mass spectrometry

Cited by 29 publications

References 43 publications

Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood

Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood

Genomic 5-mC contents in peripheral blood leukocytes were independent protective factors for coronary artery disease with a specific profile in different leukocyte subtypes

Global and gene-specific DNA methylation and hydroxymethylation in human skin exposed and not exposed to sun radiation

Contact Info

Product

Resources

About