5-羟甲基胞嘧啶及其TET氧合酶在神经系统发育和相关疾病中的研究进展

doi:10.16288/j.yczz.17-086

遗传 ›› 2017, Vol. 39 ›› Issue (12): 1138-1149.doi: 10.16288/j.yczz.17-086

5-羟甲基胞嘧啶及其TET氧合酶在神经系统发育和相关疾病中的研究进展

王建(),张凯翔,芦国珍,赵湘辉()

第四军医大学基础医学部神经生物学教研室暨脑科学协同创新中心,西安 710032

收稿日期:2017-03-13 修回日期:2017-07-01 出版日期:2017-12-20 发布日期:2017-07-25
作者简介:王建,本科,临床医学专业。研究方向：神经发育的表观遗传调控。E-mail: jianwangadc@163.com|赵湘辉，博士，副教授，研究方向：神经发育的表观遗传调控。E-mail: xianghuizhao@fmmu.edu.cn
基金资助:
国家自然科学基金(31371077,31571050);陕西省科学技术研究发展计划项目(2014KJXX-57)

Research progress on 5hmC and TET dioxygenases in neurodevelopment and neurological diseases

Jian Wang(),Kaixiang Zhang,Guozhen Lu,Xianghui Zhao()

Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China

Received:2017-03-13 Revised:2017-07-01 Online:2017-12-20 Published:2017-07-25
Supported by:
the National Natural Science Foundation of China(31371077,31571050);Shaanxi Science and Technology Research and Development Program(2014KJXX-57)

摘要/Abstract

摘要：

神经系统的正常发育是多种因素相互协调作用的结果,一旦特定因素失衡将引起相关疾病的发生。近年来不断有研究发现,DNA去甲基化过程的一类中间产物5-羟甲基胞嘧啶(5-hydroxymethylcytosine, 5hmC)作为一种新的表观遗传标记,在神经系统中高水平分布,并参与认知、记忆等重要的神经功能。5hmC的形成由氧合酶家族分子(ten-eleven translocation protein, TET)催化,在多种神经系统相关疾病中,5hmC水平和TETs分子的表达都发生改变,提示TET-5hmC表观遗传机制在复杂的神经系统发生发展过程中发挥了重要的调控作用。此外,作为基因表达调控的DNA标记物,5hmC的基因定位与基因表达水平的关系也是重要的研究方向。本文就近年来5hmC和TET家族蛋白分子在神经系统发育和相关疾病方面的重要研究发现进行了综述总结,希望为相关领域研究人员深入开展研究提供重要的思路,并为相关疾病设计治疗策略提供理论支持。

关键词: 5-羟甲基胞嘧啶, TET氧合酶, 神经发育, 神经系统疾病, 表观遗传调控

Abstract:

The development of the nervous system is coordinately regulated by multiple interacting factors. If a certain factor is altered or mutated, the coordinated developmental processes could be disrupted, resulting in neurological diseases. The 5-hydroxymethylcytosine (5hmC) is an intermediate product of the DNA demethylation processes. 5hmC and its metabolic enzymes, the ten-eleven translocation protein—TET family of dioxygenases, have recently been identified as new epigenetic players important in the regulation of the nervous system development, as well as in cognition, memory and other neurological functions. In various studies on neurodevelopment and neurodegeneration related diseases, the levels of 5hmC and TET proteins could be differentially regulated during development and/or disease pathogenesis, suggesting the potentially critical roles of 5hmC and TETs in these neural developmental and disease processes. In this review, we summarize the recent advances in research on 5hmC and TET dioxygenases in the regulation of neurodevelopment and neurological diseases, thereby providing significant insights on the involvements of 5hmC and TETs in neurodevelopment and on establishing new therapeutic strategies for human neurological diseases.

Key words: 5-hydroxymethylcytosine, TET dioxygenases, neurodevelopment, neurological diseases, epigenetic regulation

王建, 张凯翔, 芦国珍, 赵湘辉. 5-羟甲基胞嘧啶及其TET氧合酶在神经系统发育和相关疾病中的研究进展[J]. 遗传, 2017, 39(12): 1138-1149.

Jian Wang, Kaixiang Zhang, Guozhen Lu, Xianghui Zhao. Research progress on 5hmC and TET dioxygenases in neurodevelopment and neurological diseases[J]. Hereditas(Beijing), 2017, 39(12): 1138-1149.

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5-羟甲基胞嘧啶及其TET氧合酶在神经系统发育和相关疾病中的研究进展

Research progress on 5hmC and TET dioxygenases in neurodevelopment and neurological diseases

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