Structure-Based Identification of New High-Affinity Nucleosome Binding Sequences

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• 作者：Federica Battistini¹ ; Christopher A. Hunter¹ ; ^{C.Hunter@shef.ac.uk} ; Irene K. Moore² ; Jonathan Widom²
• 关键词：nucleosome ; DNA structure ; DNA bending ; protein&ndash ; DNA interaction ; energy calculation
• 刊名：Journal of Molecular Biology
• 出版年：2012
• 期刊代码：102_00222836
• 类别：imm
• 出版时间：29 June, 2012
• 卷：420
• 期：1-2
• 页码：8-16
• 文件大小：490 K

摘要

The substrate for the proteins that express genetic information in the cell is not naked DNA but an assembly of nucleosomes, where the DNA is wrapped around histone proteins. The organization of these nucleosomes on genomic DNA is influenced by the DNA sequence. Here, we present a structure-based computational approach that translates sequence information into the energy required to bend DNA into a nucleosome-bound conformation. The calculations establish the relationship between DNA sequence and histone octamer binding affinity. In silico selection using this model identified several new DNA sequences, which were experimentally found to have histone octamer affinities comparable to the highest-affinity sequences known. The results provide insights into the molecular mechanism through which DNA sequence information encodes its organization. A quantitative appreciation of the thermodynamics of nucleosome positioning and rearrangement will be one of the key factors in understanding the regulation of transcription and in the design of new promoter architectures for the purposes of tuning gene expression dynamics.