Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy
Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy
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DOI：
10.1016/j.jmb.2005.11.073
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发表时间：
2006-04-28
影响因子：
5.6
通讯作者：
Benham, C
中科院分区：
文献类型：
--
作者：
Bode, J;Winkelmann, S;Benham, C
骨架或基质附着区（S/MAR）被认为参与真核生物染色体的组织和多种DNA功能的调节。它们的特征在植物和人类之间是保守的，并且各种生物活性都与它们相关。在基因组序列中鉴定S/MAR已经被证明是出乎意料的困难，因为它们似乎没有与它们相关的共有序列或序列基序。我们已经表明，S/MAR共享一个特征性的结构特性，他们有一个显着的预测倾向，进行链分离时，放置在负超螺旋张力。这一结果与实验观察一致，S/MAR含有碱基不配对区（布尔斯）。在这里，我们进行了定量评估的压力诱导的DNA双链体不稳定（SIDD）和S/MAR结合活性之间的关联。我们首先使用合成的寡聚体来研究如何安排本地化的碱基不配对区域内的不配对元素影响S/MAR结合。以这种方式发现的组织属性被施加到调查的具体措施的压力引起的双重不稳定和自然发生的S/MAR的结合性能之间的相关性。为此，我们分析了S/MAR和非S/MAR元件，这些元件来自人类基因组或烟草基因组。我们发现，S/MAR表现出广泛的不稳定的长区域。此外，发现在均匀条件下计算的这些片段的SIDD属性的定量测量与它们的实验测量的S/MAR结合强度非常高度相关（r（2）>0.8）。这些结果表明，双链体不稳定可能参与的机制，S/MAR的功能。他们还建议，SIDD属性可以被纳入到一个改进的计算策略，以搜索基因组DNA序列的网站具有必要的属性作为S/MAR的功能，甚至估计其相对结合强度。(c)2005爱思唯尔有限公司保留所有权利。
Scaffold or matrix-attachment regions (S/MARs) are thought to be involved in the organization of eukaryotic chromosomes and in the regulation of several DNA functions. Their characteristics are conserved between plants and humans, and a variety of biological activities have been associated with them. The identification of S/MARs within genomic sequences has proved to be unexpectedly difficult, as they do not appear to have consensus sequences or sequence motifs associated with them. We have shown that S/MARs do share a characteristic structural property, they have a markedly high predicted propensity to undergo strand separation when placed under negative superhelical tension. This result agrees with experimental observations, that S/MARs contain base-unpairing regions (BURs). Here, we perform a quantitative evaluation of the association between the ease of stress-induced DNA duplex destabilization (SIDD) and S/MAR binding activity. We first use synthetic oligomers to investigate how the arrangement of localized unpairing elements within a baseunpairing region affects S/MAR binding. The organizational properties found in this way are applied to the investigation of correlations between specific measures of stress-induced duplex destabilization and the binding properties of naturally occurring S/MARs. For this purpose, we analyze S/MAR and non-S/MAR elements that have been derived from the human genome or from the tobacco genome. We find that S/MARs exhibit long regions of extensive destabilization. Moreover, quantitative measures of the SIDD attributes of these fragments calculated under uniform conditions are found to correlate very highly (r(2)>0.8) with their experimentally measured S/MAR-binding strengths. These results suggest that duplex destabilization may be involved in the mechanisms by which S/MARs function. They suggest also that SIDD properties may be incorporated into an improved computational strategy to search genomic DNA sequences for sites having the necessary attributes to function as S/MARs, and even to estimate their relative binding strengths. (c) 2005 Elsevier Ltd. All rights reserved.