Nair T Murlidharan
Department of Biological sciences, Indiana University South Bend, 1700 Mishawaka Ave, South Bend, IN-46634, USA.
BMC Struct Biol. 2010 May 17;10 Suppl 1(Suppl 1):S8. doi: 10.1186/1472-6807-10-S1-S8.
Most eukaryotic DNA contained in the nucleus is packaged by wrapping DNA around histone octamers. Histones are ubiquitous and bind most regions of chromosomal DNA. In order to achieve smooth wrapping of the DNA around the histone octamer, the DNA duplex should be able to deform and should possess intrinsic curvature. The deformability of DNA is a result of the non-parallelness of base pair stacks. The stacking interaction between base pairs is sequence dependent. The higher the stacking energy the more rigid the DNA helix, thus it is natural to expect that sequences that are involved in wrapping around the histone octamer should be unstacked and possess intrinsic curvature. Intrinsic curvature has been shown to be dictated by the periodic recurrence of certain dinucleotides. Several genome-wide studies directed towards mapping of nucleosome positions have revealed periodicity associated with certain stretches of sequences. In the current study, these sequences have been analyzed with a view to understand their sequence-dependent structures.
Higher order DNA structures and the distribution of molecular bend loci associated with 146 base nucleosome core DNA sequence from C. elegans and chicken have been analyzed using the theoretical model for DNA curvature. The curvature dispersion calculated by cyclically permuting the sequences revealed that the molecular bend loci were delocalized throughout the nucleosome core region and had varying degrees of intrinsic curvature.
The higher order structures associated with nucleosomes of C.elegans and chicken calculated from the sequences revealed heterogeneity with respect to the deviation of the DNA axis. The results points to the possibility of context dependent curvature of varying degrees to be associated with nucleosomal DNA.
细胞核中包含的大多数真核生物DNA是通过将DNA缠绕在组蛋白八聚体上进行包装的。组蛋白普遍存在并与染色体DNA的大多数区域结合。为了使DNA顺利缠绕在组蛋白八聚体上，DNA双链体应能够变形并具有内在曲率。DNA的可变形性是碱基对堆积不平行的结果。碱基对之间的堆积相互作用取决于序列。堆积能量越高，DNA螺旋越刚性，因此可以自然地预期，参与缠绕组蛋白八聚体的序列应该是未堆积的并且具有内在曲率。内在曲率已被证明由某些二核苷酸的周期性重复所决定。几项针对核小体位置图谱绘制的全基因组研究揭示了与某些序列片段相关的周期性。在当前研究中，对这些序列进行了分析，以了解它们的序列依赖性结构。
使用DNA曲率理论模型分析了与秀丽隐杆线虫和鸡的146个碱基核小体核心DNA序列相关的高阶DNA结构和分子弯曲位点的分布。通过对序列进行循环置换计算得到的曲率分散表明，分子弯曲位点在整个核小体核心区域是离域的，并且具有不同程度的内在曲率。
根据序列计算得到的与秀丽隐杆线虫和鸡的核小体相关的高阶结构显示，DNA轴的偏差存在异质性。结果表明，不同程度的上下文依赖性曲率可能与核小体DNA相关。
