Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus.
Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus.
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全基因组DNA甲基化图谱表明恒河猴胸腺衰老的潜在表观遗传调节。
DOI：
10.3390/ijms232314984
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发表时间：
2022-11-29
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
我们分析了两个年轻（1岁）和两个成年（9岁）恒河猴（Macaca mulatta）的全基因组亚硫酸氢盐测序（WGBS）和RNA测序数据，以表征胸腺基因组DNA甲基化谱，并探讨胸腺年龄相关变化的分子机制。结合两组学数据，我们确定了DNA甲基化和基因表达之间的相关性，并发现DNA甲基化在衰老胸腺的功能变化中起着至关重要的作用，特别是在免疫和凝血方面。C3和C5 AR 2的低甲基化水平和C7的高甲基化水平可能导致这些基因在成年恒河猴胸腺中的高表达，从而激活经典补体途径和旁路途径，增强其天然免疫功能。成年胸腺具有增强的凝血途径，这可能是由于7种促凝因子基因（F13 A1、CLEC 4D、CLEC 4 E、FCN 3、PDGFRA、FGF 2和FGF 7）的低甲基化和上调表达以及CPB 2的低甲基化和低表达以抑制血栓的降解。此外，成年胸腺中T细胞分化、活化和成熟的功能下降也与T细胞发育基因（CD 3G、GAD 2、ADAMDEC 1和LCK）和胸腺激素基因TMPO的甲基化水平和基因表达水平的变化密切相关。通过比较4种哺乳动物与年龄相关的甲基化基因，发现大多数表观遗传时钟具有种属特异性。此外，基于等位基因特异性DNA甲基化的基因组景观，我们确定了几个年龄相关的成簇序列依赖性等位基因特异性DNA甲基化（cS-ASM）基因。总的来说，这些DNA甲基化模式也可能有助于理解胸腺衰老与表观基因组的机制。
We analyzed whole-genome bisulfite sequencing (WGBS) and RNA sequencing data of two young (1 year old) and two adult (9 years old) rhesus macaques (Macaca mulatta) to characterize the genomic DNA methylation profile of the thymus and explore the molecular mechanism of age-related changes in the thymus. Combining the two-omics data, we identified correlations between DNA methylation and gene expression and found that DNA methylation played an essential role in the functional changes of the aging thymus, especially in immunity and coagulation. The hypomethylation levels of C3 and C5AR2 and the hypermethylation level of C7 may lead to the high expressions of these genes in adult rhesus macaque thymuses, thus activating the classical complement pathway and the alternative pathway and enhancing their innate immune function. Adult thymuses had an enhanced coagulation pathway, which may have resulted from the hypomethylation and upregulated expressions of seven coagulation-promoting factor genes (F13A1, CLEC4D, CLEC4E, FCN3, PDGFRA, FGF2 and FGF7) and the hypomethylation and low expression of CPB2 to inhibit the degradation of blood clots. Furthermore, the functional decline in differentiation, activation and maturation of T cells in adult thymuses was also closely related to the changes in methylation levels and gene expression levels of T cell development genes (CD3G, GAD2, ADAMDEC1 and LCK) and the thymogenic hormone gene TMPO. A comparison of the age-related methylated genes among four mammal species revealed that most of the epigenetic clocks were species-specific. Furthermore, based on the genomic landscape of allele-specific DNA methylation, we identified several age-related clustered sequence-dependent allele-specific DNA methylated (cS-ASM) genes. Overall, these DNA methylation patterns may also help to assist with understanding the mechanisms of the aging thymus with the epigenome.
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影响因子：
4.5
作者：
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DOI：
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发表时间：
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影响因子：
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