Effects of DNA methylation on nucleosome stability.
Effects of DNA methylation on nucleosome stability.
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DOI：
10.1093/nar/gks893
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发表时间：
2013-03-01
影响因子：
14.9
通讯作者：
Anderson JN
中科院分区：
文献类型：
--
作者：
Collings CK;Waddell PJ;Anderson JN
CpG二核苷酸的DNA甲基化是脊椎动物细胞基因表达调控中最重要的表观遗传学机制之一。在这份报告中，我们结合高通量测序对572kb的人DNA和668kb的未甲基化或甲基化的小鼠DNA进行了核小体重建实验，以研究这种表观遗传修饰对核小体定位和稳定性的影响。结果表明，由核苷酸序列定位的核小体的一个子集对甲基化敏感，修饰增加了这些序列与组蛋白八聚体的亲和力。这些核小体区别于大多数甲基化不敏感的核小体的特征是CpG二核苷酸的频率增加和CpG的独特旋转方向，使得它们的细沟倾向于朝向核小体中的组蛋白而不是远离。与内含子相比，这些甲基化敏感的核小体优先与外显子相关，而转录起始点附近的未甲基化CpG岛在甲基化后变得富含在核小体中。这项研究的结果表明，DNA甲基化对核小体稳定性的影响可以概括在细胞中观察到的情况，并提供了DNA甲基化与染色质结构和功能之间的直接联系。
Methylation of DNA at CpG dinucleotides represents one of the most important epigenetic mechanisms involved in the control of gene expression in vertebrate cells. In this report, we conducted nucleosome reconstitution experiments in conjunction with high-throughput sequencing on 572 KB of human DNA and 668 KB of mouse DNA that was unmethylated or methylated in order to investigate the effects of this epigenetic modification on the positioning and stability of nucleosomes. The results demonstrated that a subset of nucleosomes positioned by nucleotide sequence was sensitive to methylation where the modification increased the affinity of these sequences for the histone octamer. The features that distinguished these nucleosomes from the bulk of the methylation-insensitive nucleosomes were an increase in the frequency of CpG dinucleotides and a unique rotational orientation of CpGs such that their minor grooves tended to face toward the histones in the nucleosome rather than away. These methylation-sensitive nucleosomes were preferentially associated with exons as compared to introns while unmethylated CpG islands near transcription start sites became enriched in nucleosomes upon methylation. The results of this study suggest that the effects of DNA methylation on nucleosome stability in vitro can recapitulate what has been observed in the cell and provide a direct link between DNA methylation and the structure and function of chromatin.
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影响因子：
64.8
作者：
Brogaard, Kristin;Xi, Liqun;Wang, Ji-Ping;Widom, Jonathan
通讯作者：
Widom, Jonathan
影响因子：
5.6
作者：
Allan, James;Fraser, Ross M.;Owen-Hughes, Tom;Keszenman-Pereyra, David
通讯作者：
Keszenman-Pereyra, David
影响因子：
2.9
作者：
Chandler, SP;Guschin, D;Wolffe, AP
通讯作者：
Wolffe, AP
影响因子：
3.7
作者：
Collings CK;Fernandez AG;Pitschka CG;Hawkins TB;Anderson JN
通讯作者：
Anderson JN
DOI：
10.1098/rsta.1997.0002
发表时间：
1997-01-15
影响因子：
5
作者：
ElHassan, MA;Calladine, CR
通讯作者：
Calladine, CR