Regulation of chromatin folding by conformational variations of nucleosome linker DNA.
Regulation of chromatin folding by conformational variations of nucleosome linker DNA.
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DOI：
10.1093/nar/gkx562
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发表时间：
2017-09-19
影响因子：
14.9
通讯作者：
Grigoryev SA
中科院分区：
文献类型：
--
作者：
Buckwalter JM;Norouzi D;Harutyunyan A;Zhurkin VB;Grigoryev SA
接头 DNA 构象变异已被提议用于指导核小体阵列折叠成或多或少紧凑的染色质纤维，但缺乏此类模型的直接实验证据。在这里，我们通过在核小体接头的特定位置设计带有 A 束的核小体阵列来测试这一假设，以诱导接头 DNA 向内 (AT-IN) 和向外 (AT-OUT) 弯曲。使用电子显微镜和分析离心技术，我们观察到 AT-IN 核小体阵列自发折叠成高度紧凑的结构，与连接组蛋白 H1 诱导的结构相当。相反，AT-OUT核小体阵列形成不太紧凑的结构，核小体相互作用减少，类似于野生型核小体阵列。添加连接组蛋白 H1 进一步增加了 A-tract 阵列的压缩，同时保持了它们之间的结构差异。此外，限制性核酸酶消化显示紧凑型 AT-IN 阵列中核小体接头的可及性大大降低。电子显微镜分析和 3D 计算蒙特卡罗模拟与深刻的锯齿形接头 DNA 构型以及由于向内接头 DNA 弯曲而导致 AT-IN 阵列中更接近的核小体接近一致。我们提出，A-tracts 在 DNA 连接子中的进化偏好定位可能控制染色质高阶折叠，从而影响基因表达、转录和 DNA 修复等细胞过程。
Linker DNA conformational variability has been proposed to direct nucleosome array folding into more or less compact chromatin fibers but direct experimental evidence for such models are lacking. Here, we tested this hypothesis by designing nucleosome arrays with A-tracts at specific locations in the nucleosome linkers to induce inward (AT-IN) and outward (AT-OUT) bending of the linker DNA. Using electron microscopy and analytical centrifugation techniques, we observed spontaneous folding of AT-IN nucleosome arrays into highly compact structures, comparable to those induced by linker histone H1. In contrast, AT-OUT nucleosome arrays formed less compact structures with decreased nucleosome interactions similar to wild-type nucleosome arrays. Adding linker histone H1 further increased compaction of the A-tract arrays while maintaining structural differences between them. Furthermore, restriction nuclease digestion revealed a strongly reduced accessibility of nucleosome linkers in the compact AT-IN arrays. Electron microscopy analysis and 3D computational Monte Carlo simulations are consistent with a profound zigzag linker DNA configuration and closer nucleosome proximity in the AT-IN arrays due to inward linker DNA bending. We propose that the evolutionary preferred positioning of A-tracts in DNA linkers may control chromatin higher-order folding and thus influence cellular processes such as gene expression, transcription and DNA repair.
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DOI：
10.1073/pnas.0903280106
发表时间：
2009-08-11
影响因子：
11.1
作者：
Grigoryev, Sergei A.;Arya, Gaurav;Schlick, Tamar
通讯作者：
Schlick, Tamar
影响因子：
5.6
作者：
Huynh, VAT;Robinson, PJJ;Rhodes, D
通讯作者：
Rhodes, D
影响因子：
2.9
作者：
KOO, HS;DRAK, J;CROTHERS, DM
通讯作者：
CROTHERS, DM
影响因子：
4.3
作者：
Bajpai G;Jain I;Inamdar MM;Das D;Padinhateeri R
通讯作者：
Padinhateeri R
DOI：
10.1073/pnas.91.24.11621
发表时间：
1994-11-22
影响因子：
11.1
作者：
LEUBA, SH;YANG, GL;BUSTAMANTE, C
通讯作者：
BUSTAMANTE, C