Co-regulation of histone-modifying enzymes in cancer.
Co-regulation of histone-modifying enzymes in cancer.
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DOI：
10.1371/journal.pone.0024023
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Benevolenskaya EV
中科院分区：
文献类型：
--
作者：
Islam AB;Richter WF;Jacobs LA;Lopez-Bigas N;Benevolenskaya EV
癌症的特征在于多个基因表达的异常模式。基因表达的这些主要变化被认为不仅是由于遗传变化，而且是由于表观遗传变化。表观遗传变化是通过化学修饰，包括组蛋白修饰。然而，目前还不清楚组蛋白修饰蛋白与基因组区域的结合以及组蛋白修饰的放置是否有效地将相应的基因与人类基因组中的其余基因区分开来。我们进行了组蛋白去甲基化酶（HDMs）和组蛋白甲基转移酶（HMTs）的基因表达分析，它们的靶基因和相关组蛋白修饰的基因在正常和肿瘤组织。令人惊讶的是，该分析揭示了不同HDM和HMT的表达水平存在相关性。观察到的HDM/HMT基因表达特征对特定的正常和癌细胞类型是特异性的，并且与靶基因表达和具有组蛋白修饰的基因的表达高度相关。值得注意的是，我们观察到赖氨酸4和赖氨酸27的三甲基化分离了优先表达和低表达的基因，这在癌细胞中与正常细胞相比是惊人的不同。我们的结论是，在协调调节酶执行组蛋白修饰的变化可能是全球发生在癌症的表观遗传变化的基础。
Cancer is characterized by aberrant patterns of expression of multiple genes. These major shifts in gene expression are believed to be due to not only genetic but also epigenetic changes. The epigenetic changes are communicated through chemical modifications, including histone modifications. However, it is unclear whether the binding of histone-modifying proteins to genomic regions and the placing of histone modifications efficiently discriminates corresponding genes from the rest of the genes in the human genome. We performed gene expression analysis of histone demethylases (HDMs) and histone methyltransferases (HMTs), their target genes and genes with relevant histone modifications in normal and tumor tissues. Surprisingly, this analysis revealed the existence of correlations in the expression levels of different HDMs and HMTs. The observed HDM/HMT gene expression signature was specific to particular normal and cancer cell types and highly correlated with target gene expression and the expression of genes with histone modifications. Notably, we observed that trimethylation at lysine 4 and lysine 27 separated preferentially expressed and underexpressed genes, which was strikingly different in cancer cells compared to normal cells. We conclude that changes in coordinated regulation of enzymes executing histone modifications may underlie global epigenetic changes occurring in cancer.
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影响因子：
4.3
作者：
Islam, Abul B. M. M. K.;Richter, William F.;Benevolenskaya, Elizaveta V.
通讯作者：
Benevolenskaya, Elizaveta V.
体细胞突变改变生发中心起源的滤泡性和弥漫性大 B 细胞淋巴瘤中的 EZH2 (Tyr641)。
影响因子：
30.8
作者：
Morin, Ryan D.;Johnson, Nathalie A.;Severson, Tesa M.;Mungall, Andrew J.;An, Jianghong;Goya, Rodrigo;Paul, Jessica E.;Boyle, Merrill;Woolcock, Bruce W.;Kuchenbauer, Florian;Yap, Damian;Humphries, R. Keith;Griffith, Obi L.;Shah, Sohrab;Zhu, Henry;Kimbara, Michelle;Shashkin, Pavel;Charlot, Jean F.;Tcherpakov, Marianna;Corbett, Richard;Tam, Angela;Varhol, Richard;Smailus, Duane;Moksa, Michelle;Zhao, Yongjun;Delaney, Allen;Qian, Hong;Birol, Inanc;Schein, Jacqueline;Moore, Richard;Holt, Robert;Horsman, Doug E.;Connors, Joseph M.;Jones, Steven;Aparicio, Samuel;Hirst, Martin;Gascoyne, Randy D.;Marra, Marco A.
通讯作者：
Marra, Marco A.
DOI：
10.1038/nrc2931
发表时间：
2010-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
37.3
作者：
Cao, Paul;Deng, Zhiyong;Sui, Guangchao
通讯作者：
Sui, Guangchao
影响因子：
64.5
作者：
Christensen, Jesper;Agger, Karl;Helin, Kristian
通讯作者：
Helin, Kristian