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首页> 外文期刊>The FEBS journal >DNA methylation-mediated nucleosome dynamics and oncogenic Ras signaling: insights from FAS, FAS ligand and RASSF1A
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DNA methylation-mediated nucleosome dynamics and oncogenic Ras signaling: insights from FAS, FAS ligand and RASSF1A

机译：DNA甲基化介导的核小体动力学和致癌Ras信号传导：FAS，FAS配体和RASSF1A的见解

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摘要

Cytosine methylation at the 5-carbon position is the only known stable base modification found in the mammalian genome. The organization and modification of chromatin is a key factor in programming gene expression patterns. Recent findings suggest that DNA methylation at the junction of transcription initiation and elongation plays a critical role in suppression of transcription. This effect is mechanistically mediated by the state of chromatin modification. DNA methylation attracts binding of methyl-CpG-binding domain proteins that trigger repression of transcription, whereas DNA demethylation facilitates transcription activation. Understanding the rules that guide differential gene expression, as well as transcription dynamics and transcript abundance, has proven to be a taxing problem for molecular biologists and oncologists alike. The use of novel molecular modeling methods is providing exciting insights into the challenging problem of how methylation mediates chromatin dynamics. New data implicate lipid rafts as the coordinators of signals emanating from the cell membrane and are converging on the mechanisms linking DNA methylation and chromatin dynamics. This review focuses on some of these recent advances and uses lipid-raft-facilitated Ras signaling as a paradigm for understanding DNA methylation, chromatin dynamics and apoptosis.
机译：在5-碳位置的胞嘧啶甲基化是在哺乳动物基因组中发现的唯一已知的稳定碱基修饰。染色质的组织和修饰是编程基因表达模式的关键因素。最近的发现表明，在转录起始和延伸的交界处的DNA甲基化在抑制转录中起关键作用。该效应是由染色质修饰状态机械地介导的。 DNA甲基化吸引甲基CpG结合域蛋白的结合，从而触发转录抑制，而DNA脱甲基化则促进转录激活。对于分子生物学家和肿瘤学家而言，了解指导差异基因表达以及转录动力学和转录本丰度的规则已被证明是一个艰巨的问题。新颖的分子建模方法的使用为甲基化如何介导染色质动力学的挑战性问题提供了令人兴奋的见解。新数据暗示脂质筏是从细胞膜发出的信号的协调者，并且正在集中于连接DNA甲基化和染色质动力学的机制。这篇综述聚焦于这些最新进展中的一些，并使用脂质筏促进的Ras信号作为理解DNA甲基化，染色质动力学和细胞凋亡的范例。

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