5-hydroxymethylcytosine is highly dynamic across human fetal brain development.
5-hydroxymethylcytosine is highly dynamic across human fetal brain development.
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DOI：
10.1186/s12864-017-4091-x
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发表时间：
2017-09-18
期刊：
影响因子：
4.4
通讯作者：
Mill J
中科院分区：
文献类型：
--
作者：
Spiers H;Hannon E;Schalkwyk LC;Bray NJ;Mill J
表观遗传过程在人类中枢神经系统发育过程中的转录调控中起着关键作用。我们之前描述了在人类胎儿大脑发育过程中DNA甲基化(5mC)的动态变化，但在此期间操作的其他表观遗传过程尚未被广泛探索。特别令人感兴趣的是DNA羟甲基化(5hmC)，这是一种在人脑中丰富的修饰，被认为在神经元功能、学习和记忆中发挥重要作用。在这项研究中，我们对71个人胎脑样本的基因组中的5HmC进行了量化，这些样本的时间跨度为怀孕后23到184天。我们发现，在人脑发育过程中，5hmC发生了广泛的变化，胎儿脑中5hmC存在显著的性别差异，以及特定部位5mC和5hmC之间的相互作用。最后，我们确定了胎儿大脑中5hmC与遗传变异相关的基因座。这项研究首次对人类神经发育过程中5hmC的动态变化进行了系统分析，并强调了这种修饰在人脑中的潜在重要性。我们的胎脑5hmC数据的可搜索数据库可作为资源提供给http://www.epigenomicslab.com/online-data-resources.的研究社区本文DOI：(10.1186/s12864-0174091-x)的在线版本包含补充材料，授权用户可以使用。
Epigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation (5mC) occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory. In this study, we quantify 5hmC across the genome of 71 human fetal brain samples spanning 23 to 184 days post-conception. We identify widespread changes in 5hmC occurring during human brain development, notable sex-differences in 5hmC in the fetal brain, and interactions between 5mC and 5hmC at specific sites. Finally, we identify loci where 5hmC in the fetal brain is associated with genetic variation. This study represents the first systematic analysis of dynamic changes in 5hmC across human neurodevelopment and highlights the potential importance of this modification in the human brain. A searchable database of our fetal brain 5hmC data is available as a resource to the research community at http://www.epigenomicslab.com/online-data-resources. The online version of this article doi:(10.1186/s12864-017-4091-x) contains supplementary material, which is available to authorized users.
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