DNA 甲基化对核小体结构的影响。
Effects of DNA methylation on the structure of nucleosomes.
机构信息
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
出版信息
J Am Chem Soc. 2012 Jan 11;134(1):173-5. doi: 10.1021/ja210273w. Epub 2011 Dec 15.
Nucleosomes are the fundamental packing units of the eukaryotic genome. Understanding the dynamic structure of a nucleosome is a key to the elucidation of genome packaging in eukaryotes, which is tied to the mechanisms of gene regulation. CpG methylation of DNA is an epigenetic modification associated with the inactivation of transcription and the formation of a repressive chromatin structure. Unraveling the changes in the structure of nucleosomes upon CpG methylation is an essential step toward the understanding of the mechanisms of gene repression and silencing by CpG methylation. Here we report single-molecule and ensemble fluorescence studies showing how the structure of a nucleosome is affected by CpG methylation. The results indicate that CpG methylation induces tighter wrapping of DNA around the histone core accompanied by a topology change. These findings suggest that changes in the physical properties of nucleosomes induced upon CpG methylation may contribute directly to the formation of a repressive chromatin structure.
核小体是真核生物基因组的基本包装单元。了解核小体的动态结构是阐明真核生物基因组包装的关键，这与基因调控的机制有关。DNA 的 CpG 甲基化是一种与转录失活和形成抑制性染色质结构相关的表观遗传修饰。揭示 CpG 甲基化后核小体结构的变化是理解 CpG 甲基化抑制基因表达和沉默机制的重要步骤。在这里，我们报告了单分子和整体荧光研究结果，展示了 CpG 甲基化如何影响核小体的结构。结果表明，CpG 甲基化诱导 DNA 更紧密地缠绕在组蛋白核心周围，并伴有拓扑结构变化。这些发现表明，CpG 甲基化诱导的核小体物理性质的变化可能直接导致抑制性染色质结构的形成。
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