Institute of Computer Science, Polish Academy of Sciences, 01-248 Warsaw, Poland.
Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.
Int J Mol Sci. 2019 Jul 15;20(14):3478. doi: 10.3390/ijms20143478.
During the last two decades, several international consortia have been established to unveil the molecular background of human cancers including gliomas. As a result, a huge outbreak of new genetic and epigenetic data appeared. It was not only shown that gliomas share some specific DNA sequence aberrations, but they also present common alterations of chromatin. Many researchers have reported specific epigenetic features, such as DNA methylation and histone modifications being involved in tumor pathobiology. Unlike mutations in DNA, epigenetic changes are more global in nature. Moreover, many studies have shown an interplay between different types of epigenetic changes. Alterations in DNA methylation in gliomas are one of the best described epigenetic changes underlying human pathology. In the following work, we present the state of knowledge about global DNA methylation patterns in gliomas and their interplay with histone modifications that may affect transcription factor binding, global gene expression and chromatin conformation. Apart from summarizing the impact of global DNA methylation on glioma pathobiology, we provide an extract of key mechanisms of DNA methylation machinery.
在过去的二十年中，成立了几个国际财团，旨在揭示包括神经胶质瘤在内的人类癌症的分子背景。结果，大量新的遗传和表观遗传数据出现了。不仅表明神经胶质瘤具有一些特定的 DNA 序列异常，而且还存在染色质的常见改变。许多研究人员报告了特定的表观遗传特征，例如 DNA 甲基化和组蛋白修饰参与肿瘤病理生物学。与 DNA 突变不同，表观遗传变化在性质上更加全局性。此外，许多研究表明不同类型的表观遗传变化之间存在相互作用。神经胶质瘤中的 DNA 甲基化改变是人类病理学中描述最好的表观遗传改变之一。在下面的工作中，我们介绍了神经胶质瘤中全局 DNA 甲基化模式及其与组蛋白修饰相互作用的最新知识，这些修饰可能会影响转录因子结合、全局基因表达和染色质构象。除了总结全局 DNA 甲基化对神经胶质瘤病理生物学的影响外，我们还提供了 DNA 甲基化机制的关键机制摘要。
