Department of Chemistry, New York University, New York, NY 10003, USA.
J Mol Biol. 2010 Nov 12;403(5):777-802. doi: 10.1016/j.jmb.2010.07.057. Epub 2010 Aug 13.
Chromatin fibers encountered in various species and tissues are characterized by different nucleosome repeat lengths (NRLs) of the linker DNA connecting the nucleosomes. While single cellular organisms and rapidly growing cells with high protein production have short NRL ranging from 160 to 189 bp, mature cells usually have longer NRLs ranging between 190 and 220 bp. Recently, various experimental studies have examined the effect of NRL on the internal organization of chromatin fiber. Here, we investigate by mesoscale modeling of oligonucleosomes the folding patterns for different NRL, with and without linker histone (LH), under typical monovalent salt conditions using both one-start solenoid and two-start zigzag starting configurations. We find that short to medium NRL chromatin fibers (173 to 209 bp) with LH condense into zigzag structures and that solenoid-like features are viable only for longer NRLs (226 bp). We suggest that medium NRLs are more advantageous for packing and various levels of chromatin compaction throughout the cell cycle than their shortest and longest brethren; the former (short NRLs) fold into narrow fibers, while the latter (long NRLs) arrays do not easily lead to high packing ratios due to possible linker DNA bending. Moreover, we show that the LH has a small effect on the condensation of short-NRL arrays but has an important condensation effect on medium-NRL arrays, which have linker lengths similar to the LH lengths. Finally, we suggest that the medium-NRL species, with densely packed fiber arrangements, may be advantageous for epigenetic control because their histone tail modifications can have a greater effect compared to other fibers due to their more extensive nucleosome interaction network.
在不同物种和组织中遇到的染色质纤维的特征是连接核小体的连接 DNA 的核小体重复长度（NRL）不同。虽然单细胞生物和具有高蛋白质产生的快速生长的细胞具有短的 NRL，范围从 160 到 189 bp，成熟细胞通常具有较长的 NRL，范围在 190 到 220 bp 之间。最近，各种实验研究已经检查了 NRL 对染色质纤维内部组织的影响。在这里，我们使用单核小体和双螺旋起始的起始构型，在典型的单价盐条件下，通过寡核小体的介观建模研究了不同 NRL 的折叠模式，有无连接组蛋白（LH）。我们发现，带有 LH 的短至中等 NRL 染色质纤维（173 到 209 bp）凝结成锯齿状结构，只有较长的 NRL（226 bp）才具有类似螺旋的特征。我们认为，在细胞周期中，中 NRL 比最短和最长的 NRL 更有利于包装和各种水平的染色质紧缩；前者（短 NRL）折叠成狭窄的纤维，而后者（长 NRL）阵列由于可能的连接 DNA 弯曲不易导致高包装比。此外，我们表明，LH 对短 NRL 阵列的浓缩有很小的影响，但对中 NRL 阵列有重要的浓缩作用，中 NRL 阵列的连接长度与 LH 长度相似。最后，我们认为，具有密集纤维排列的中 NRL 物种可能有利于表观遗传控制，因为与其他纤维相比，其组蛋白尾部修饰可以产生更大的影响，因为它们具有更广泛的核小体相互作用网络。
