Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure.
Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure.
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DOI：
10.1371/journal.pcbi.1005365
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发表时间：
2017-01
影响因子：
4.3
通讯作者：
Padinhateeri R
中科院分区：
文献类型：
--
作者：
Bajpai G;Jain I;Inamdar MM;Das D;Padinhateeri R
为什么大多数体内实验都没有发现30纳米的染色质纤维，在体外研究得很好，这是一个谜。对于理解30 nm纤维的结构至关重要的两个基本物理输入是连接DNA的刚度和DNA进入/退出核小体的相对取向。基于这些输入，我们模拟了染色质结构，并表明结合并局部弯曲接头DNA的非组蛋白蛋白的存在破坏了任何规则的高级结构（例如，之字形）。考虑到nhp 6和HMG-B等蛋白质的弯曲几何形状，我们的理论预测了染色质结构的相图，该相图是DNA弯曲非组蛋白蛋白密度和平均接头DNA长度的函数。对于广泛的连接器长度，我们表明，当我们改变一个参数，即，弯曲的连接器区域由于非组蛋白的分数，稳态结构将显示从锯齿形过渡到一个不规则的结构，这是让人想起最近在实验中观察到的结构。我们的理论可以解释最近在体内观察到的不规则染色质的有限分数的相邻（i + 2）和相邻（i + 1）核小体相互作用的共存。细胞的命运不仅取决于遗传密码，还取决于蛋白质结合DNA（称为染色质）的3D组织的性质。染色质包装被认为是以分层的方式，并且包装中的关键阶段之一被认为具有30 nm的特定宽度的锯齿形结构。然而，最近的大多数实验未能发现活细胞中染色质的锯齿状有序排列。在这项工作中，我们解决了这个难题，并认为任何规则的，有序的，包装的染色质是不可行的，因为某些类型的蛋白质可以结合和弯曲的染色体DNA。
Why most of the in vivo experiments do not find the 30-nm chromatin fiber, well studied in vitro, is a puzzle. Two basic physical inputs that are crucial for understanding the structure of the 30-nm fiber are the stiffness of the linker DNA and the relative orientations of the DNA entering/exiting nucleosomes. Based on these inputs we simulate chromatin structure and show that the presence of non-histone proteins, which bind and locally bend linker DNA, destroys any regular higher order structures (e.g., zig-zag). Accounting for the bending geometry of proteins like nhp6 and HMG-B, our theory predicts phase-diagram for the chromatin structure as a function of DNA-bending non-histone protein density and mean linker DNA length. For a wide range of linker lengths, we show that as we vary one parameter, that is, the fraction of bent linker region due to non-histone proteins, the steady-state structure will show a transition from zig-zag to an irregular structure—a structure that is reminiscent of what is observed in experiments recently. Our theory can explain the recent in vivo observation of irregular chromatin having co-existence of finite fraction of the next-neighbor (i + 2) and neighbor (i + 1) nucleosome interactions. The fate of a cell is not just decided by the genetic code but also by the nature of the 3D organization of the protein-bound DNA, known as chromatin. Chromatin packaging is believed to be in a hierarchical manner, and one of the crucial stages in the packaging is argued to be having a zig-zag structure with specific width of 30 nm. However, most of the recent experiments failed to find any zig-zag-like ordered arrangement of chromatin in living cells. In this work, we address this puzzle, and argue that any regular, ordered, packaging of chromatin is unviable given that certain types of proteins can bind and bend the chromosomal DNA.