Sexually divergent DNA methylation patterns with hippocampal aging.
Sexually divergent DNA methylation patterns with hippocampal aging.
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DOI：
10.1111/acel.12681
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发表时间：
2017-12
期刊：
影响因子：
7.8
通讯作者：
Freeman WM
中科院分区：
文献类型：
--
作者：
Masser DR;Hadad N;Porter HL;Mangold CA;Unnikrishnan A;Ford MM;Giles CB;Georgescu C;Dozmorov MG;Wren JD;Richardson A;Stanford DR;Freeman WM
DNA甲基化是基因组功能的中心调节器，甲基化模式的改变表明生物衰老和死亡。与年龄相关的海马体细胞、生化和分子变化会导致认知障碍和对神经退行性疾病的更大脆弱性，这在性别之间存在差异。随着年龄的增长，海马表观基因组变化在这些过程中的作用尚不清楚，因为在对照动物模型中，没有对年龄相关甲基化变化的全基因组分析考虑了性别因素。幼龄（3个月）和老年（24个月）雄性和雌性小鼠海马的高深度、全基因组亚硫酸盐测序显示，虽然基因组甲基化总量不随年龄变化，但CG和非CG （CH）背景下的特定位点显示，甲基化的增加或减少与年龄相关，主要是性别差异。CG和CH位点随年龄的差异甲基化在基因间和内含子区域富集，而在两性的启动子、CG岛和特定增强子区域中表现不足，这表明某些基因组元件随着年龄的增长尤其不稳定，即使确切的基因组位点改变主要是性别特异性的。还观察到CG和CH位点常染色体甲基化的终生性别差异。在人类数据中证实了CG位点缺乏全基因组低甲基化、性分化的衰老反应和常染色体性别差异。这些数据表明，随着年龄的增长，性别是海马表观基因组变化的一个以前未被认识到的中心因素。总的来说，这些数据证明了DNA甲基化与性别、胞嘧啶背景、基因组位置和甲基化水平有关的复杂调节。
DNA methylation is a central regulator of genome function, and altered methylation patterns are indicative of biological aging and mortality. Age‐related cellular, biochemical, and molecular changes in the hippocampus lead to cognitive impairments and greater vulnerability to neurodegenerative disease that varies between the sexes. The role of hippocampal epigenomic changes with aging in these processes is unknown as no genome‐wide analyses of age‐related methylation changes have considered the factor of sex in a controlled animal model. High‐depth, genome‐wide bisulfite sequencing of young (3 month) and old (24 month) male and female mouse hippocampus revealed that while total genomic methylation amounts did not change with aging, specific sites in CG and non‐CG (CH) contexts demonstrated age‐related increases or decreases in methylation that were predominantly sexually divergent. Differential methylation with age for both CG and CH sites was enriched in intergenic and intronic regions and under‐represented in promoters, CG islands, and specific enhancer regions in both sexes, suggesting that certain genomic elements are especially labile with aging, even if the exact genomic loci altered are predominantly sex‐specific. Lifelong sex differences in autosomal methylation at CG and CH sites were also observed. The lack of genome‐wide hypomethylation, sexually divergent aging response, and autosomal sex differences at CG sites was confirmed in human data. These data reveal sex as a previously unappreciated central factor of hippocampal epigenomic changes with aging. In total, these data demonstrate an intricate regulation of DNA methylation with aging by sex, cytosine context, genomic location, and methylation level.
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影响因子：
12.3
作者：
Bell CG;Xia Y;Yuan W;Gao F;Ward K;Roos L;Mangino M;Hysi PG;Bell J;Wang J;Spector TD
通讯作者：
Spector TD
影响因子：
7.8
作者：
Jones MJ;Goodman SJ;Kobor MS
通讯作者：
Kobor MS
影响因子：
13.6
作者：
Pal S;Tyler JK
通讯作者：
Tyler JK
DOI：
10.1038/nrg2719
发表时间：
2010-03
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
12.3
作者：
Horvath S
通讯作者：
Horvath S