Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution.
Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution.
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DOI：
10.1186/s12864-015-1875-8
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发表时间：
2015-09-03
期刊：
影响因子：
4.4
通讯作者：
Turecki G
中科院分区：
文献类型：
--
作者：
Gross JA;Pacis A;Chen GG;Barreiro LB;Ernst C;Turecki G
最近发现，甲基化胞嘧啶被10 - 11易位酶家族转化为5-羟甲基化胞嘧啶（5 hmC），这一表观遗传标记的基因组定位、在不同组织中的丰度、推定的功能和稳定性引起了人们的极大兴趣。5 hmC在大脑中起着关键作用，在发育过程中它特别丰富和动态。在这里，我们全面表征5 hmC在前额叶皮层的24名受试者。我们发现，尽管在无关个体中5 hmC含量存在个体间差异，但在常染色体上约8%的CpG含有5 hmC，而性染色体上含有的CpG远少于5 hmC。我们的数据还提供了证据表明5 hmC具有转录调节特性，因为5 hmC的密度在增强子区域和外显子内最高。此外，我们链接增加5 hmC密度组蛋白修饰结合位点，积极转录基因的基因体，和外显子-内含子边界。最后，我们提供了几个感兴趣的基因组区域，包含性别特异性5 hmC。总的来说，这些结果为越来越多的研究提供了重要的参考，这些研究对研究5 hmC在大脑和精神疾病中的作用感兴趣。本文的在线版本（doi：10.1186/s12864-015-1875-8）包含补充材料，可供授权用户使用。
The recent discovery that methylated cytosines are converted to 5-hydroxymethylated cytosines (5hmC) by the family of ten-eleven translocation enzymes has sparked significant interest on the genomic location, the abundance in different tissues, the putative functions, and the stability of this epigenetic mark. 5hmC plays a key role in the brain, where it is particularly abundant and dynamic during development. Here, we comprehensively characterize 5hmC in the prefrontal cortices of 24 subjects. We show that, although there is inter-individual variability in 5hmC content among unrelated individuals, approximately 8 % of all CpGs on autosomal chromosomes contain 5hmC, while sex chromosomes contain far less. Our data also provide evidence suggesting that 5hmC has transcriptional regulatory properties, as the density of 5hmC was highest in enhancer regions and within exons. Furthermore, we link increased 5hmC density to histone modification binding sites, to the gene bodies of actively transcribed genes, and to exon-intron boundaries. Finally, we provide several genomic regions of interest that contain gender-specific 5hmC. Collectively, these results present an important reference for the growing number of studies that are interested in the investigation of the role of 5hmC in brain and mental disorders. The online version of this article (doi:10.1186/s12864-015-1875-8) contains supplementary material, which is available to authorized users.