Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains.
Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains.
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DOI：
10.1038/nn.3588
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发表时间：
2014-01
影响因子：
25
通讯作者：
Casaccia, Patrizia
中科院分区：
文献类型：
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作者：
Huynh, Jimmy L.;Garg, Paras;Thin, Tin Htwe;Yoo, Seungyeul;Dutta, Ranjan;Trapp, Bruce D.;Haroutunian, Vahram;Zhu, Jun;Donovan, Michael J.;Sharp, Andrew J.;Casaccia, Patrizia
使用Illumina 450K阵列和严格的年龄和性别校正统计分析，我们报告了来自人类多发性硬化症患者和对照组大脑的无病理区域的DNA甲基化在全基因组范围内的差异。差异是微妙的，但在一个独立的验证队列中广泛和可重复。差异DNA甲基化的转录后果通过全基因组rna测序分析进一步确定，并在两个独立的队列中得到验证。调节少突胶质细胞存活的基因，如BCL2L2和NDRG1，在多发性硬化症影响的大脑中被高甲基化，表达水平低于对照组，而与蛋白水解加工相关的基因（如LGMN， CTSZ）被低甲基化，表达水平较高。这些结果不是由于多发性硬化症患者和对照组之间细胞组成的差异。因此，影响少突胶质细胞对损伤易感性的基因的表观基因组变化在多发性硬化症影响的大脑无病理区域被检测到。
Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis–affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independent cohorts. Genes regulating oligodendrocyte survival, such as BCL2L2 and NDRG1, were hypermethylated and expressed at lower levels in multiple sclerosis–affected brains than in controls, while genes related to proteolytic processing (for example, LGMN, CTSZ) were hypomethylated and expressed at higher levels. These results were not due to differences in cellular composition between multiple sclerosis and controls. Thus, epigenomic changes in genes affecting oligodendrocyte susceptibility to damage are detected in pathology-free areas of multiple sclerosis–affected brains.
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影响因子：
3.5
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
通讯作者：
Mill J
影响因子：
4
作者：
Jevnikar, Zala;Obermajer, Natasa;Kos, Janko
通讯作者：
Kos, Janko
影响因子：
6.4
作者：
Graumann, U;Reynolds, R;Schaeren-Wiemers, N
通讯作者：
Schaeren-Wiemers, N
影响因子：
5.8
作者：
Hedstrom, A. K.;Baarnhielm, M.;Alfredsson, L.
通讯作者：
Alfredsson, L.
影响因子：
64.8
作者：
通讯作者：
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