Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis.
Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis.
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DOI：
10.1038/srep24587
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发表时间：
2016-04-15
影响因子：
4.6
通讯作者：
Chen HF
中科院分区：
文献类型：
--
作者：
Zhang J;Luo H;Liu H;Ye W;Luo R;Chen HF
组蛋白修饰在基因调控和基因表达中起着关键作用。TRIM24作为组蛋白阅读器可以识别组蛋白修饰。然而，TRIM24与组蛋白修饰之间的特异性识别机制尚未解决。本文采用基于分子动力学模拟的动力学关联网络系统生物学方法来回答这一问题。我们的网络分析表明，H3K23ac的动力学相关网络与野生型和其他修饰的动力学相关网络明显不同。然后提出了“协同修饰诱导识别”的假说，将组蛋白修饰与TRIM24结合联系起来。这些观察结果进一步证实了突变和网络扰动网络的社区分析。最后，基于H3K23ac的最短路径搜索，还确定了可能的识别途径。由于甲基化和乙酰化修饰，不同系统之间的识别途径存在显著差异。本文的分析和其他研究表明，基于动态网络的分析可能是一个有用的一般策略，研究蛋白质翻译后修饰和相关的识别的生物学。
Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.