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魏姝, 华海蓉, 陈千权, 张莹, 陈菲, 李树清, 李凡, 李家立. 2017: 树鼩大脑发育和老化过程中DNA去甲基化修饰的动态变化特征. 动物学研究, 38(2): 96-102. DOI: 10.24272/j.issn.2095-8137.2017.013
引用本文: 魏姝, 华海蓉, 陈千权, 张莹, 陈菲, 李树清, 李凡, 李家立. 2017: 树鼩大脑发育和老化过程中DNA去甲基化修饰的动态变化特征. 动物学研究, 38(2): 96-102. DOI: 10.24272/j.issn.2095-8137.2017.013
Shu Wei, Hai-Rong Hua, Qian-Quan Chen, Ying Zhang, Fei Chen, Shu-Qing Li, Fan Li, Jia-Li Li. 2017: Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri chinensis) brain during postnatal development and aging. Zoological Research, 38(2): 96-102. DOI: 10.24272/j.issn.2095-8137.2017.013
Citation: Shu Wei, Hai-Rong Hua, Qian-Quan Chen, Ying Zhang, Fei Chen, Shu-Qing Li, Fan Li, Jia-Li Li. 2017: Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri chinensis) brain during postnatal development and aging. Zoological Research, 38(2): 96-102. DOI: 10.24272/j.issn.2095-8137.2017.013

树鼩大脑发育和老化过程中DNA去甲基化修饰的动态变化特征

Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri chinensis) brain during postnatal development and aging

  • 摘要: 大脑的发育生长和老化过程与多个表观遗传调控系统密切相关。其中就包括DNA甲基化和去甲基化的动态变化。在本研究中,我们观察了在树鼩大脑发育生长和老化过程中TET家族酶介导的DNA去甲基化中间产物5-羟甲基化胞嘧啶(5hmC)的动态变化特征和潜在的影响作用。结果表明,在树鼩大脑发育生长过程中,5hmC水平主要表现为渐进性升高;在大脑老化过程中,多个脑区包括新皮层的前额叶、顶叶、枕叶和海马的神经元内5hmC出现显著地减低,但是这一现象并没有显著地发生在小脑区域。进一步研究发现,TET家族酶TET2号TET3的表达水平变化与5hmC变化一致,推测它们的表达和功能变化可能是决定5hmC动态变化的关键因素。我们的研究揭示了树鼩大脑发育和老化过程中5hmC的变化具有明显地时空特异性,为下一步利用树鼩对象,探讨脑发育和老化的机理、以及神经系统疾病的相关科学问题提供了新的方向。

     

    Abstract: Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews (Tupaia belangeri chinensis). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.

     

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