Chiu Tsu-Pei, Yang Lin, Zhou Tianyin, Main Bradley J, Parker Stephen C J, Nuzhdin Sergey V, Tullius Thomas D, Rohs Remo
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Departments of Computational Medicine and Bioinformatics and Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Nucleic Acids Res. 2015 Jan;43(Database issue):D103-9. doi: 10.1093/nar/gku977. Epub 2014 Oct 17.
Many regulatory mechanisms require a high degree of specificity in protein-DNA binding. Nucleotide sequence does not provide an answer to the question of why a protein binds only to a small subset of the many putative binding sites in the genome that share the same core motif. Whereas higher-order effects, such as chromatin accessibility, cooperativity and cofactors, have been described, DNA shape recently gained attention as another feature that fine-tunes the DNA binding specificities of some transcription factor families. Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species.
许多调控机制在蛋白质与DNA结合方面需要高度特异性。核苷酸序列无法回答为何一种蛋白质仅与基因组中众多具有相同核心基序的假定结合位点中的一小部分结合这一问题。尽管诸如染色质可及性、协同作用和辅因子等高阶效应已被描述，但DNA形状最近作为另一个微调某些转录因子家族DNA结合特异性的特征而受到关注。我们的DNA形状注释基因组浏览器（GBshape；可从http://rohslab.cmb.usc.edu/GBshape/免费获取）提供了94种生物整个基因组的小沟宽度、螺旋桨扭转、滚动、螺旋扭转和羟基自由基切割预测。使用GBshape框架可以轻松添加其他基因组。GBshape可用于以基因组浏览器轨道格式定性可视化DNA形状注释，并以核苷酸分辨率下载作为基因组位置函数的DNA形状特征定量值。作为生物学应用，我们展示了人类、果蝇和蠕虫核小体占据序列中存在的DNA形状特征的周期性，并证明了四种果蝇物种基因组中转录起始位点之间的结构相似性。
