• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Epigenetics & Chromatin >Absence of genomic hypomethylation or regulation of cytosine-modifying enzymes with aging in male and female mice
【24h】

Absence of genomic hypomethylation or regulation of cytosine-modifying enzymes with aging in male and female mice

机译：雄性和雌性小鼠中缺乏基因组低甲基化或胞嘧啶修饰酶的调节与衰老

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Changes to the epigenome with aging, and DNA modifications in particular, have been proposed as a central regulator of the aging process, a predictor of mortality, and a contributor to the pathogenesis of age-related diseases. In the central nervous system, control of learning and memory, neurogenesis, and plasticity require changes in cytosine methylation and hydroxymethylation. Although genome-wide decreases in methylation with aging are often reported as scientific dogma, primary research reports describe decreases, increases, or lack of change in methylation and hydroxymethylation and their principle regulators, DNA methyltransferases and ten-eleven translocation dioxygenases in the hippocampus. Furthermore, existing data are limited to only male animals. Results Through examination of the hippocampus in young, adult, and old male and female mice by antibody-based, pyrosequencing, and whole-genome oxidative bisulfite sequencing methods, we provide compelling evidence that contradicts the genomic hypomethylation theory of aging. We also demonstrate that expression of DNA methyltransferases and ten-eleven translocation dioxygenases is not differentially regulated with aging or between the sexes, including the proposed cognitive aging regulator DNMT3a2. Using oxidative bisulfite sequencing that discriminates methylation from hydroxymethylation and by cytosine (CG and non-CG) context, we observe sex differences in average CG methylation and hydroxymethylation of the X chromosome, and small age-related differences in hydroxymethylation of CG island shores and shelves, and methylation of promoter regions. Conclusion These findings clarify a long-standing misconception of the epigenomic response to aging and demonstrate the need for studies of base-specific methylation and hydroxymethylation with aging in both sexes.
机译：背景技术随着年龄的增长，表观基因组的变化，特别是DNA的修饰，已被提出作为衰老过程的中央调节器，死亡率的预测因子以及与年龄有关的疾病的发病机理的贡献者。在中枢神经系统中，控制学习和记忆，神经发生和可塑性需要改变胞嘧啶甲基化和羟甲基化。尽管全基因组甲基化随着年龄的增长而减少是科学教条，但主要研究报告描述了甲基化和羟甲基化及其主要调控因子，DNA海马中的DNA甲基转移酶和11-11个易位双加氧酶的减少，增加或缺乏变化。此外，现有数据仅限于雄性动物。结果通过基于抗体，焦磷酸测序和全基因组氧化亚硫酸氢盐测序方法对成年，成年和成年雄性和雌性小鼠的海马进行检查，我们提供了令人信服的证据，与衰老的基因组低甲基化理论相矛盾。我们还表明，DNA甲基转移酶和十一个11易位双加氧酶的表达不随年龄或两性之间的差异而受到调节，包括拟议的认知衰老调节剂DNMT3a2。使用氧化亚硫酸氢盐测序来区分甲基化与羟甲基化和胞嘧啶（CG和非CG），我们观察到X染色体平均CG甲基化和羟甲基化的性别差异，以及CG岛海岸和架子的羟甲基化的年龄相关性差异小和启动子区域的甲基化。结论这些发现澄清了长期以来对衰老的表观基因组反应的误解，并表明有必要研究男女性别与衰老有关的碱基特异性甲基化和羟甲基化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号