Changing chromatin fiber conformation by nucleosome repositioning.
Changing chromatin fiber conformation by nucleosome repositioning.
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DOI：
10.1016/j.bpj.2014.09.026
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发表时间：
2014-11
影响因子：
3.4
通讯作者：
Oliver Müller;Nick Kepper;R. Schöpflin;Ramona Ettig;K. Rippe;Gero Wedemann
中科院分区：
文献类型：
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作者：
Oliver Müller;Nick Kepper;R. Schöpflin;Ramona Ettig;K. Rippe;Gero Wedemann
染色质构象相对于核小体位置是动态的和异质的，这可以通过细胞中的染色质重塑复合物来改变。这些分子机器水解ATP以移位或驱逐核小体，并建立具有规则和更不规则间隔的核小体以及核小体耗尽区域的基因座。核小体重新定位对三维染色质结构的影响知之甚少。在这里，我们解决这个问题，通过使用一个粗粒度的计算机模型阵列的101个核小体考虑几个染色质纤维模型与和不连接组蛋白，分别。我们研究了折叠链的依赖于中央核小体的位置，通过改变相邻的连接DNA的长度在碱基对步骤。我们在模拟中发现，这些易位对染色质纤维的形状和性质有很强的影响：i）中心的纤维曲率和柔性大大增加，并且促进了链上远处核小体之间的长距离接触。ii），纤维构象的最高不稳定性发生在核小体从规则间距移动两个碱基对时，而与DNA螺旋扭曲同相的10 bp的接头DNA变化的影响是最小的。iii）纤维构象可以稳定核小体的规则间距，因为促进了核小体之间的有利堆叠相互作用。这可以对抗核小体易位并增加染色质重塑的能量成本。我们的计算建模框架使得有可能描述核小体位置方面的染色质的构象异质性，从而推进理论模型，以更好地理解基因组压缩和访问如何在细胞内进行调节。
Chromatin conformation is dynamic and heterogeneous with respect to nucleosome positions, which can be changed by chromatin remodeling complexes in the cell. These molecular machines hydrolyze ATP to translocate or evict nucleosomes, and establish loci with regularly and more irregularly spaced nucleosomes as well as nucleosome-depleted regions. The impact of nucleosome repositioning on the three-dimensional chromatin structure is only poorly understood. Here, we address this issue by using a coarse-grained computer model of arrays of 101 nucleosomes considering several chromatin fiber models with and without linker histones, respectively. We investigated the folding of the chain in dependence of the position of the central nucleosome by changing the length of the adjacent linker DNA in basepair steps. We found in our simulations that these translocations had a strong effect on the shape and properties of chromatin fibers: i), Fiber curvature and flexibility at the center were largely increased and long-range contacts between distant nucleosomes on the chain were promoted. ii), The highest destabilization of the fiber conformation occurred for a nucleosome shifted by two basepairs from regular spacing, whereas effects of linker DNA changes of ∼10 bp in phase with the helical twist of DNA were minimal. iii), A fiber conformation can stabilize a regular spacing of nucleosomes inasmuch as favorable stacking interactions between nucleosomes are facilitated. This can oppose nucleosome translocations and increase the energetic costs for chromatin remodeling. Our computational modeling framework makes it possible to describe the conformational heterogeneity of chromatin in terms of nucleosome positions, and thus advances theoretical models toward a better understanding of how genome compaction and access are regulated within the cell.