5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients.
5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients.
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DOI：
10.1038/ncomms13177
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发表时间：
2016-11-25
影响因子：
16.6
通讯作者：
Christensen, Brock C.
中科院分区：
文献类型：
--
作者：
Johnson, Kevin C.;Houseman, E. Andres;King, Jessica E.;von Herrmann, Katharine M.;Fadul, Camilo E.;Christensen, Brock C.
胶质母细胞瘤表现出广泛的分子改变，包括高度扭曲的表观基因组。在这里，我们解决了全基因组5-甲基胞嘧啶和5-羟甲基胞嘧啶胶质母细胞瘤通过平行处理的DNA与亚硫酸氢盐和氧化亚硫酸氢盐处理。我们应用统计算法从甲基化阵列数据估计5-甲基胞嘧啶、5-羟甲基胞嘧啶和未甲基化的比例。我们发现，5-羟甲基胞嘧啶是耗尽胶质母细胞瘤相比，前额叶皮质组织。此外，胶质母细胞瘤中5-羟甲基胞嘧啶的基因组定位与动态细胞身份调节的特征相关，例如组织特异性转录和超级增强子。5-羟甲基胞嘧啶基因组分布的注释揭示了与RNA调控过程、免疫功能、干细胞维持和驱动细胞增殖的转录因子的结合位点的显著关联。此外，基于模型的聚类结果表明，具有低5-羟甲基胞嘧啶模式的患者具有显著较差的总生存期。我们的研究结果表明，5-羟甲基胞嘧啶模式与转录密切相关，定位于疾病关键基因，并与患者预后相关。 胶质母细胞瘤具有扭曲的表观基因组。在这里，作者比较了胶质母细胞瘤和前额叶皮层组织中5-甲基胞嘧啶和5-羟甲基胞嘧啶的全基因组谱，报告了这些谱与患者预后之间的相关性。
Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue. In addition, the genomic localization of 5-hydroxymethylcytosine in glioblastoma is associated with features of dynamic cell-identity regulation such as tissue-specific transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic distribution reveal significant associations with RNA regulatory processes, immune function, stem cell maintenance and binding sites of transcription factors that drive cellular proliferation. In addition, model-based clustering results indicate that patients with low-5-hydroxymethylcytosine patterns have significantly poorer overall survival. Our results demonstrate that 5-hydroxymethylcytosine patterns are strongly related with transcription, localizes to disease-critical genes and are associated with patient prognosis. Glioblastomas have distorted epigenomes. Here, the authors compare the genome-wide profiles of 5-methylcytosine and 5- hydroxymethylcytosine in glioblastoma and prefrontal cortex tissue reporting a correlation between these profiles and patients' prognosis.
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肿瘤基因对神经元和星形胶质细胞的去分化会在小鼠中诱导神经胶质瘤。
DOI：
10.1126/science.1226929
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Friedmann-Morvinski D;Bushong EA;Ke E;Soda Y;Marumoto T;Singer O;Ellisman MH;Verma IM
通讯作者：
Verma IM
影响因子：
3.8
作者：
Dedeurwaerder, Sarah;Defrance, Matthieu;Fuks, Francois
通讯作者：
Fuks, Francois
DOI：
10.1056/nejmoa1407279
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eckel-Passow JE;Lachance DH;Molinaro AM;Walsh KM;Decker PA;Sicotte H;Pekmezci M;Rice T;Kosel ML;Smirnov IV;Sarkar G;Caron AA;Kollmeyer TM;Praska CE;Chada AR;Halder C;Hansen HM;McCoy LS;Bracci PM;Marshall R;Zheng S;Reis GF;Pico AR;O'Neill BP;Buckner JC;Giannini C;Huse JT;Perry A;Tihan T;Berger MS;Chang SM;Prados MD;Wiemels J;Wiencke JK;Wrensch MR;Jenkins RB
通讯作者：
Jenkins RB
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
5.8
作者：
Akalin, Altuna;Franke, Vedran;Schuebeler, Dirk
通讯作者：
Schuebeler, Dirk