Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome.
Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome.
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DOI：
10.1093/nar/gku1305
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发表时间：
2015-01
影响因子：
14.9
通讯作者：
Bird AP
中科院分区：
文献类型：
--
作者：
Illingworth RS;Gruenewald-Schneider U;De Sousa D;Webb S;Merusi C;Kerr AR;James KD;Smith C;Walker R;Andrews R;Bird AP
DNA甲基化的改变可能是发育、衰老和疾病易感性的机械性驱动因素，这一点得到了广泛承认，但证据仍然参差不齐或不确定。在这方面特别令人感兴趣的是大脑，据报道，DNA甲基化对神经元活动、学习和记忆、药物成瘾和神经退化有影响。然而，直到最近，人们对人脑甲基组的“景观”知之甚少。在这里，我们分析了代表不同个体和大脑区域的43个大脑样本中的190万个CPG。与所有其他区域相比，小脑是一个一致的异常值，并显示了超过16000个差异甲基化区域(DMR)。出乎意料的是，小脑中低甲基化和高甲基化区域的序列特征截然不同。相比之下，很少有DMR区分皮质、边缘系统和脑干的区域。在这些地区很容易发现个体间的DMR。这些结果得出了一个令人惊讶的结论，即除了小脑之外，同一个体不同大脑区域之间的DNA甲基化模式比不同个体之间单个大脑区域的DNA甲基化模式更加同质。这一发现表明，人类大脑DNA甲基组的主要决定因素是DNA序列组成，而不是发育状态。
The possibility that alterations in DNA methylation are mechanistic drivers of development, aging and susceptibility to disease is widely acknowledged, but evidence remains patchy or inconclusive. Of particular interest in this regard is the brain, where it has been reported that DNA methylation impacts on neuronal activity, learning and memory, drug addiction and neurodegeneration. Until recently, however, little was known about the ‘landscape’ of the human brain methylome. Here we assay 1.9 million CpGs in each of 43 brain samples representing different individuals and brain regions. The cerebellum was a consistent outlier compared to all other regions, and showed over 16 000 differentially methylated regions (DMRs). Unexpectedly, the sequence characteristics of hypo- and hypermethylated domains in cerebellum were distinct. In contrast, very few DMRs distinguished regions of the cortex, limbic system and brain stem. Inter-individual DMRs were readily detectable in these regions. These results lead to the surprising conclusion that, with the exception of cerebellum, DNA methylation patterns are more homogeneous between different brain regions from the same individual, than they are for a single brain region between different individuals. This finding suggests that DNA sequence composition, not developmental status, is the principal determinant of the human brain DNA methylome.
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影响因子：
16
作者：
Skene, Peter J.;Illingworth, Robert S.;Webb, Shaun;Kerr, Alastair R. W.;James, Keith D.;Turner, Daniel J.;Andrews, Rob;Bird, Adrian P.
通讯作者：
Bird, Adrian P.
影响因子：
14.9
作者：
Sunkin SM;Ng L;Lau C;Dolbeare T;Gilbert TL;Thompson CL;Hawrylycz M;Dang C
通讯作者：
Dang C
影响因子：
30.8
作者：
Kerkel, Kristi;Spadola, Alexandra;Tycko, Benjamin
通讯作者：
Tycko, Benjamin
影响因子：
4.5
作者：
Gertz J;Varley KE;Reddy TE;Bowling KM;Pauli F;Parker SL;Kucera KS;Willard HF;Myers RM
通讯作者：
Myers RM
影响因子：
34.7
作者：
Robison, Alfred J.;Nestler, Eric J.
通讯作者：
Nestler, Eric J.