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Modeling studies of chromatin fiber structure as a function of DNA linker length.

机译:染色质纤维结构作为DNA接头长度的函数的模型研究。

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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.
机译:在各种物种和组织中遇到的染色质纤维的特征在于,连接核小体的接头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产量的快速生长的细胞具有较短的NRL,范围从160到189 bp,但成熟细胞通常具有较长的NRL,范围在190和220 bp之间。最近,各种实验研究已经检验了NRL对染色质纤维内部组织的影响。在这里,我们通过寡核苷酸的中尺度建模研究了在典型的一价盐条件下使用一键螺线管和两键锯齿形起始构型在不同的NRL(有和没有接头组蛋白(LH)的情况下)的折叠模式。我们发现,具有LH的中短NRL染色质纤维(173至209 bp)会凝结为锯齿形结构,类似螺线管的特征仅适用于较长的NRL(226 bp)。我们建议,中等的NRL比最短和最长的兄弟更适合包装和整个细胞周期中各种水平的染色质压实;前者(短NRLs)折叠成窄纤维,而后者(长NRLs)阵列由于可能的接头DNA弯曲而不容易导致高堆积率。此外,我们显示LH对短NRL阵列的凝聚作用较小,但对中等NRL阵列具有重要的凝聚作用,后者的连接子长度与LH长度相似。最后,我们认为具有密集排列的纤维排列的中性NRL物种可能对表观遗传控制有利,因为与其他纤维相比,由于其更广泛的核小体相互作用网络,它们的组蛋白尾部修饰可能具有更大的作用。

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