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首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood
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Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood

机译：与纵向小鼠血液中的与年龄相关的外延甲基甲基DNA甲基化和羟甲基甲基化

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摘要

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.
机译：在胞嘧啶 - 磷酸盐 - 鸟嘌呤（CPG）中的DNA甲基化因人类和动物模型的年龄的函数而变化，这是一种可能导致慢性病发育的过程。最近的研究已经研究了DNA甲基化 - 5-羟甲基胞嘧啶（5HMC）的氧化形式的作用 - 在表观蛋白酶中，但其对与年龄相关的DNA甲基化的贡献仍不清楚。我们测试了5HMC随龄为5HMC变化的假设，但在与5-甲基胞嘧啶（5MC）相反的方向上，可能在衰老中发挥明显的作用。为了表征外膜脑老化，使用两种测序方法的纵向血液样品（2,4和10个月）在纵向血液样本（2,4和10个月）中测量基因组5MC和5HMC - 增强了均硫酸氢盐测序和羟甲基化DNA免疫沉淀测序。通过年龄检查表观蛋白酶，我们鉴定了28,196个独特的差异甲基化CpG（DMC）和8,613个差异羟甲基化区域（DHMRS）。小鼠血液显示出外膜内聚甲基化的一般模式和随龄衰老。比较年龄相关的DMC和DHMRS，1,854个注释基因显示差异5MC和5HMC，包括一个基因 - NFIC - 在相同的250bp染色体区域中的五个CpG。在该地区，5MC和5HMC水平随着年龄的增长而降低。反映这些年龄相关的表观遗传变化，血液中的NFIC RNA表达随着年龄的增长而降低，表明该基因的年龄相关调节可以由5HMC驱动，而不是规范DNA甲基化。结合，我们的基因组结果显示年龄相关的差异5MC和5HMC，以及某些证据，其中5HMC变化可能会推动与年龄相关的DNA甲基化和基因表达。

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