Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals.
Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals.
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DOI：
10.1038/tp.2017.93
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发表时间：
2017-05-09
影响因子：
6.8
通讯作者：
Turecki G
中科院分区：
文献类型：
--
作者：
Gross JA;Pacis A;Chen GG;Drupals M;Lutz PE;Barreiro LB;Turecki G
5-羟甲基胞嘧啶（5-Hydroxymethylcytosine, 5hmC）是最近发现的一种表观遗传标记，在脑组织中特别丰富，并调节基因转录。我们最近开始了解5hmC在大脑发育、可塑性和疾病中的重要作用，但目前关于5hmC在精神疾病中的改变的数据很少。在这里，我们报告了我们认为是抑郁症大脑中5hmC的第一个全基因组分析。使用AbaSI测序，我们研究了抑郁症患者（N=19）和精神健康对照组（N=19）前额叶皮层中的5hmC。与之前对其他表型的全球5hmC分析一致，可能是由于5hmC含量的个体间差异，5hmC在染色体和基因组特征上的分布在群体之间没有差异。然而，我们确实发现了550个CpGs具有不同羟甲基化的暗示性证据。其中，我们利用靶向氧化亚硫酸盐测序验证了肌球蛋白XVI （MYO16）和胰岛素降解酶基因体中的CpGs。此外，5hmC的富集也与抑郁自杀中这两个基因的表达变化有关。总之，我们的研究结果提出了一种将5hmC增加与抑郁症联系起来的新机制，并为该领域的未来研究提供了框架。
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19). Consistent with previous global 5hmC analyses in other phenotypes, and likely owing to the inter-individual variability in 5hmC content, the distribution of 5hmC across chromosomes and genomic features was not different between groups. We did, however, find 550 CpGs with suggestive evidence of differential hydroxymethylation. Of these, we validated CpGs in the gene body of myosin XVI (MYO16) and insulin-degrading enzyme using targeted oxidative bisulfite sequencing. Furthermore, the enrichment of 5hmC was also associated with changes in the expression of these two genes in depressed suicides. Together, our results present a novel mechanism linking increased 5hmC to depression and provide a framework for future research in this field.
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影响因子：
4.4
作者：
Gross JA;Pacis A;Chen GG;Barreiro LB;Ernst C;Turecki G
通讯作者：
Turecki G
影响因子：
6.8
作者：
Maheu M;Lopez JP;Crapper L;Davoli MA;Turecki G;Mechawar N
通讯作者：
Mechawar N
影响因子：
3.5
作者：
KUROCHKIN, IV;GOTO, S
通讯作者：
GOTO, S
影响因子：
5.7
作者：
Brasa S;Mueller A;Jacquemont S;Hahne F;Rozenberg I;Peters T;He Y;McCormack C;Gasparini F;Chibout SD;Grenet O;Moggs J;Gomez-Mancilla B;Terranova R
通讯作者：
Terranova R
影响因子：
4.3
作者：
Al-Mahdawi S;Virmouni SA;Pook MA
通讯作者：
Pook MA