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从计算机模拟中理解表观遗传 DNA 甲基化与核小体定位之间的联系。

Understanding the connection between epigenetic DNA methylation and nucleosome positioning from computer simulations.

机构信息

Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain ; Joint IRB-BSC Program in Computational Biology, Barcelona, Spain.

出版信息

PLoS Comput Biol. 2013;9(11):e1003354. doi: 10.1371/journal.pcbi.1003354. Epub 2013 Nov 21.

Abstract

Cytosine methylation is one of the most important epigenetic marks that regulate the process of gene expression. Here, we have examined the effect of epigenetic DNA methylation on nucleosomal stability using molecular dynamics simulations and elastic deformation models. We found that methylation of CpG steps destabilizes nucleosomes, especially when these are placed in sites where the DNA minor groove faces the histone core. The larger stiffness of methylated CpG steps is a crucial factor behind the decrease in nucleosome stability. Methylation changes the positioning and phasing of the nucleosomal DNA, altering the accessibility of DNA to regulatory proteins, and accordingly gene functionality. Our theoretical calculations highlight a simple physical-based explanation on the foundations of epigenetic signaling.

摘要

胞嘧啶甲基化是调控基因表达过程的最重要的表观遗传标记之一。在这里,我们使用分子动力学模拟和弹性变形模型研究了表观遗传 DNA 甲基化对核小体稳定性的影响。我们发现 CpG 步骤的甲基化会使核小体不稳定,尤其是当这些 CpG 步骤位于 DNA 小沟面向组蛋白核心的位置时。甲基化 CpG 步骤的较大刚性是核小体稳定性降低的关键因素。甲基化改变了核小体 DNA 的定位和相位,改变了 DNA 对调控蛋白的可及性,从而影响基因功能。我们的理论计算强调了一种基于简单物理原理的关于表观遗传信号的解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe8f/3836855/805de9d7f885/pcbi.1003354.g001.jpg

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