Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions
Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions
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DOI：
10.1073/pnas.0903280106
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发表时间：
2009-08-11
影响因子：
11.1
通讯作者：
Schlick, Tamar
中科院分区：
文献类型：
--
作者：
Grigoryev, Sergei A.;Arya, Gaurav;Schlick, Tamar
染色质纤维的结构确定了转录和其他模板指导的生物过程的DNA可及性，但仍未知。在这里，我们研究了30 nm染色质纤维的内部组织，将核小体链折叠的蒙特卡洛模拟与EM辅助核小体相互作用捕获（EMANIC）结合在一起。我们表明，在单价离子的生理浓度下，接头组蛋白会导致紧密的2启动锯齿形，由交替的核小体（I +/- 2）之间的相互作用主导，并由组蛋白N-Tails密封。二价离子通过促进某些接头DNA中的弯曲，从而提高顺序核小体相互作用（I +/- 1），从而进一步紧凑了纤维。值得注意的是，直链和弯曲器DNA构象都保留在完全紧凑的染色质纤维中，如EMANIC和建模所推断。这种构象变异性在能量上是有利的，因为它有助于适应纤维轴内的DNA交叉点。因此，我们的结果表明，2启动的曲折拓扑和定义螺线管模型的接头DNA弯曲类型可能同时存在于结构上异形的染色质纤维中，直径均匀30 nm。我们的数据还表明，接头组蛋白和体内二价阳离子的动态接头DNA弯曲可能会介导离散30 nm纤维内的紧密核小体堆积与自我相关的高阶染色体形式之间的过渡。
The architecture of the chromatin fiber, which determines DNA accessibility for transcription and other template-directed biological processes, remains unknown. Here we investigate the internal organization of the 30-nm chromatin fiber, combining Monte Carlo simulations of nucleosome chain folding with EM-assisted nucleosome interaction capture (EMANIC). We show that at physiological concentrations of monovalent ions, linker histones lead to a tight 2-start zigzag dominated by interactions between alternate nucleosomes (i +/- 2) and sealed by histone N-tails. Divalent ions further compact the fiber by promoting bending in some linker DNAs and hence raising sequential nucleosome interactions (i +/- 1). Remarkably, both straight and bent linker DNA conformations are retained in the fully compact chromatin fiber as inferred from both EMANIC and modeling. This conformational variability is energetically favorable as it helps accommodate DNA crossings within the fiber axis. Our results thus show that the 2-start zigzag topology and the type of linker DNA bending that defines solenoid models may be simultaneously present in a structurally heteromorphic chromatin fiber with uniform 30 nm diameter. Our data also suggest that dynamic linker DNA bending by linker histones and divalent cations in vivo may mediate the transition between tight nucleosome packing within discrete 30-nm fibers and self-associated higher-order chromosomal forms.