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

Kochmanski, Joseph; Marchlewicz, Elizabeth H.; Cavalcante, Raymond G.; Sartor, Maureen A.; Dolinoy, Dana C.

doi:10.1080/15592294.2018.1507198

Cited by 29 publications

(23 citation statements)

References 66 publications

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“…Therefore, it is understandable that DNA methylation level was higher in TYO sh. Similar result also reported in mouse, which blood showed a general pattern of epigenome-wide hypermethylation with age [43]. The DNA hypermethylation in TYO sh may be involved in the epigenetic reprogramming during development, which is important in regulate gene expression [44,45].…”

Section: Discussionsupporting

confidence: 85%

Genome-Wide DNA Methylation Variations Between Grass Carp with Different Ages

Zhu

Chu

et al. 2020

Preprint

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Background: Grass carp is an important farmed fish in China that infected by many pathogens, especially grass carp reovirus (GCRV). Notably, grass carp showed age-dependent susceptibility to GCRV, while the mechanism remains unclear. Herein, we performed a genome-wide survey of differences in DNA methylation and gene expression between five months old grass carp (FMO, sensitive to GCRV) and three years old grass carp (TYO, resistant to GCRV) aim to uncover the mechanism.Results: Colorimetric quantification revealed global methylation level of TYO fish was higher than that of FMO fish. Whole-genome bisulfite sequencing (WGBS) of two groups revealed 6,214 differentially methylated regions (DMRs) and 4,052 differentially methylated genes (DMGs), with most of DMRs and DMGs showed hypermethylation patterns in TYO fish. Correlation analysis indicated that DNA hypomethylation in promoter negative correlated with gene expression, whereas positive correlation was found between gene-body DNA hypermethylation and gene expression. Enrichment analysis revealed that promoter hypo-DMGs in TYO fish were significant enriched in pathways involved in immune response while gene-body hyper-DMGs in TYO fish were significant enriched in terms related to RNA transcription, biosynthetic, and energy production. RNA-seq indicated these terms or pathways involved in immune response, biosynthetic, and energy production also significant enriched for the up-regulated genes in TYO fish. Conclusions: Collectively, these results revealed the genome-wide DNA methylation variations between grass carp with different ages. DNA methylation and gene expression variations in genes involved in immune response, biosynthetic, and energy production may contributed to the age-dependent susceptibility to GCRV in grass carp. Our results will provide important information for the disease-resistant breeding programs of grass carp and may also benefit to the research of age-dependent diseases in human.

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Section: Discussionsupporting

confidence: 85%

Genome-Wide DNA Methylation Variations Between Grass Carp with Different Ages

Zhu

Chu

et al. 2020

Preprint

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“…Only one study has examined perinatal BPA exposure effects on liver histone modifications, and the effect of these modifications on gene expression and liver function were not reported 44 . In contrast to the little that is known regarding the impact of epigenome:environment interactions on histone modifications, aging-associated changes in DNA methylation (DNAm-aging) have become well-established since the original studies of Horvath 45 , and reflect the impact of both environmental exposures and pathophysiological processes 41,[46][47][48][49][50][51] . Previous studies have assessed epigenetic signatures in rodent and human liver during normal aging by assessing DNAm-aging [52][53][54][55] .…”

Section: Discussionmentioning

confidence: 99%

Epigenome environment interactions accelerate epigenomic aging and unlock metabolically restricted epigenetic reprogramming in adulthood

et al. 2020

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Our early-life environment has a profound influence on developing organs that impacts metabolic function and determines disease susceptibility across the life-course. Using a rat model for exposure to an endocrine disrupting chemical (EDC), we show that early-life chemical exposure causes metabolic dysfunction in adulthood and reprograms histone marks in the developing liver to accelerate acquisition of an adult epigenomic signature. This epigenomic reprogramming persists long after the initial exposure, but many reprogrammed genes remain transcriptionally silent with their impact on metabolism not revealed until a later life exposure to a Western-style diet. Diet-dependent metabolic disruption was largely driven by reprogramming of the Early Growth Response 1 (EGR1) transcriptome and production of metabolites in pathways linked to cholesterol, lipid and one-carbon metabolism. These findings demonstrate the importance of epigenome:environment interactions, which early in life accelerate epigenomic aging, and later in adulthood unlock metabolically restricted epigenetic reprogramming to drive metabolic dysfunction.

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“…Rates of 5hmC were then natural log (ln) transformed to achieve a normal distribution for the linear regression analysis, which was used to examine the association between categorized BPA exposure and 5hmC. Age, smoking, alcohol consumption, and history of disease, which had been reported to be associated with 5hmC [39,40,41], were adjusted for as potential confounders.…”

Section: Methodsmentioning

confidence: 99%

Bisphenol A Exposure and Sperm ACHE Hydroxymethylation in Men

Song

Miao

Zhou

et al. 2019

IJERPH

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Exposure to bisphenol A (BPA) has been shown to impact human sperm quality. The epigenetic mechanisms underlying the effect remain unknown. The acetylcholinesterase (ACHE) gene is a sperm-expressed gene encoding the acetylcholine hydrolyzing enzyme acetylcholinesterase and participates in the apoptosis of cells, including sperm. This study aimed to examine whether BPA exposure is associated with the hydroxymethylation level of the sperm ACHE gene. A total of 157 male factory workers were studied, among whom 74 had BPA exposure in the workplace (BPA exposure group) and 83 had no BPA exposure in the workplace (control group). Urine samples were collected for BPA measurement and semen samples were collected to assay for ACHE hydroxymethylation. Sperm ACHE hydroxymethylation level was higher in the BPA exposure group (p = 0.041) compared to the control group. When subjects were categorized according to tertiles of detected BPA level, higher ACHE hydroxymethylation levels were observed for the lowest, middle, and top tertiles compared to those with BPA below the limit of detection (LOD). In a linear regression analysis adjusted for confounders, a positive linear association between urine BPA concentration and 5-hydroxymethylcytosine (5hmC) rate of the sperm ACHE gene was observed, although the association did not reach statistical significance in all categories after being stratified by the BPA tertile. In conclusion, 5hmC of the sperm ACHE gene was positively associated with BPA exposure, which may provide supportive evidence for BPA’s effects on male fertility or other health endpoints.

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

Cited by 29 publications

References 66 publications

Genome-Wide DNA Methylation Variations Between Grass Carp with Different Ages

Genome-Wide DNA Methylation Variations Between Grass Carp with Different Ages

Epigenome environment interactions accelerate epigenomic aging and unlock metabolically restricted epigenetic reprogramming in adulthood

Bisphenol A Exposure and Sperm ACHE Hydroxymethylation in Men

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