Sequence motifs and free energies of selected natural and non-natural nucleosome positioning DNA sequences
Sequence motifs and free energies of selected natural and non-natural nucleosome positioning DNA sequences
复制标题
DOI：
10.1006/jmbi.1999.2686
复制
发表时间：
1999-04-30
影响因子：
5.6
通讯作者：
Widom, J
中科院分区：
文献类型：
--
作者：
Thåström, A;Lowary, PT;Widom, J
我们的实验室最近完成了SELEX实验，从整个小鼠基因组或更多样化的化学合成随机序列DNA中分离出最有利于或不有利于核小体形成和定位的DNA序列。这里我们直接比较这些选定的自然序列和非自然序列。我们发现最强的自然定位序列对组蛋白结合和核小体形成的亲和力比许多选择的非自然序列低六倍或更多。我们得出结论，即使真核生物基因组的最高亲和力序列区域也没有进化到最高亲和力或核小体定位能力。对所选自然序列的傅里叶变换计算揭示了核小体定位的特殊意义，该基序由类似于10 bp的TA二核苷酸步骤周期放置组成。周期性TA步骤对组蛋白结合和核小体形成的贡献比其他周期性步骤(如AA （=TT), CC (=GG)）更重要，比其他YR步骤（CA （=TG）和CG）更重要，据报道，它们在蛋白质- dna复合物中具有更大的构象灵活性，甚至比TA。我们报告了用于测量未来可能被分离的更强定位序列的自由能的改进程序的发展，并表明当组蛋白- dna相互作用的有利自由能变得足够大时，基于广泛使用的交换方法的测量变得不可靠。(C) 1999学术出版社。
Our laboratories recently completed SELEX experiments to isolate DNA sequences that most-strongly favor or disfavor nucleosome formation and positioning, from the entire mouse genome or from even more diverse pools of chemically synthetic random sequence DNA. Here we directly compare these selected natural and non-natural sequences. We find that the strongest natural positioning sequences have affinities for histone binding and nucleosome formation that are sixfold or more lower than those possessed by many of the selected non-natural sequences. We conclude that even the highest-affinity sequence regions of eukaryotic genomes are not evolved for the highest affinity or nucleosome positioning power. Fourier transform calculations on the selected natural sequences reveal a special significance for nucleosome positioning of a motif consisting of similar to 10 bp periodic placement of TA dinucleotide steps. Contributions to histone binding and nucleosome formation from periodic TA steps are more significant than those from other periodic steps such as AA (=TT), CC (=GG) and more important than those from the other YR steps (CA (=TG) and CG), which are reported to have greater conformational flexibility in protein-DNA complexes even than TA. We report the development of improved procedures for measuring the free energies of even stronger positioning sequences that may be isolated in the future, and show that when the favorable free energy of histone-DNA interactions becomes sufficiently large, measurements based on the widely used exchange method become unreliable. (C) 1999 Academic Press.