5-Hydroxymethylcytosine Marks Postmitotic Neural Cells in the Adult and Developing Vertebrate Central Nervous System
5-Hydroxymethylcytosine Marks Postmitotic Neural Cells in the Adult and Developing Vertebrate Central Nervous System
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DOI：
10.1002/cne.24077
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发表时间：
2017-02-15
影响因子：
2.5
通讯作者：
Kah, Olivier
中科院分区：
文献类型：
--
作者：
Diotel, Nicolas;Merot, Yohann;Kah, Olivier
表观遗传标记5-羟甲基胞嘧啶（5-hydroxymethylcytosine, 5hmC）是哺乳动物中枢神经系统中大量存在的胞嘧啶修饰物，是由5-甲基胞嘧啶被TET酶氧化而产生的。这种标记被认为在染色质结构和基因表达的调控中起关键作用。然而，它的确切功能仍然知之甚少，关于它在非哺乳动物物种中的分布信息仍然缺乏。本研究对比研究了5hmC在成年斑马鱼、非洲爪蛙和小鼠脑内的分布。我们发现斑马鱼神经元具有高水平的5hmC，而静止或增殖的神经祖细胞具有低至检测不到的修饰胞嘧啶水平。在爪蟾幼虫和幼崽的大脑中，神经元中也检测到5hmC，而脑室增殖细胞不显示这种表观遗传标记。同样，与发育中的小鼠皮层脑室区的神经祖细胞相比，5hmC在神经元中富集。有趣的是，在小鼠神经元中，5hmC与甲基化的DNA结合蛋白MeCP2和活性染色质组蛋白修饰H3K4me2共定位。综上所述，我们的研究结果显示了5hmC在鱼类和四足动物大脑中的进化保守分布，并加强了5hmC在脊椎动物神经元中发挥控制染色质活性主要功能的观点。(C) 2016 Wiley期刊公司
The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in the regulation of chromatin structure and gene expression. However, its precise functions still remain poorly understood and information about its distribution in non-mammalian species is still lacking. Here, the distribution of 5hmC was investigated in the brain of adult zebrafish, African claw frog, and mouse in a comparative manner. We show that zebrafish neurons are endowed with high levels of 5hmC, whereas quiescent or proliferative neural progenitors show low to undetectable levels of the modified cytosine. In the brain of larval and juvenile Xenopus, 5hmC is also detected in neurons, while ventricular proliferative cells do not display this epigenetic mark. Similarly, 5hmC is enriched in neurons compared to neural progenitors of the ventricular zone in the mouse developing cortex. Interestingly, 5hmC colocalized with the methylated DNA binding protein MeCP2 and with the active chromatin histone modification H3K4me2 in mouse neurons. Taken together, our results show an evolutionarily conserved cerebral distribution of 5hmC between fish and tetrapods and reinforce the idea that 5hmC fulfills major functions in the control of chromatin activity in vertebrate neurons. (C) 2016 Wiley Periodicals, Inc.