Topological polymorphism of nucleosome fibers and folding of chromatin.-猫眼课题宝

DOI：

10.1016/j.bpj.2021.01.008

发表时间：

2021-02-16

期刊：

Biophysical journal

影响因子：

3.4

通讯作者：

中科院分区：

生物学3区

文献类型：

作者：

Zhurkin VB;Norouzi D

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896024/

我们讨论了最近观察到的多态性染色质包装在寡核小体水平，并比较它们与计算机模拟。我们的计算揭示了两个拓扑结构不同的30 nm双头纤维构象家族，其区别在于连接体长度L;具有L <$10n和L <$10n +5碱基对的纤维的每个核小体的DNA连接数分别为ΔLk <$-1.5和-1.0（其中n是自然数）。虽然之前已经观察到ΔLk = 1.5的纤维，但ΔLk = 1.0的拓扑异构体是新的。这些预测证实了精确定位的核小体的圆形核小体阵列的实验。我们认为染色质的拓扑多态性可能在转录中发挥作用，{10 n +5}纤维产生转录能力的染色质结构。这一假设与酵母菌的现有数据一致，部分与苍蝇的数据一致。我们表明，必须考虑两种纤维拓扑异构体（ΔLk = −1.5和−1.0）来解释使用新技术获得的实验数据：全基因组Micro-C，Hi-CO和RICC-seq，以及体外核小体阵列的自缔合。这些拓扑异构体的相对稳定性可能取决于调节核小体间相互作用强度的表观遗传组蛋白修饰。潜在地，我们的发现可能反映了基因组功能不同部分保留拓扑学上不同的高阶结构的一般趋势。

We discuss recent observations of polymorphic chromatin packaging at the oligonucleosomal level and compare them with computer simulations. Our computations reveal two topologically different families of two-start 30-nm fiber conformations distinguished by the linker length L; fibers with L ≈ 10n and L ≈ 10n+5 basepairs have DNA linking numbers per nucleosome of ΔLk ≈ −1.5 and −1.0, respectively (where n is a natural number). Although fibers with ΔLk ≈ −1.5 were observed earlier, the topoisomer with ΔLk ≈ −1.0 is novel. These predictions were confirmed experimentally for circular nucleosome arrays with precisely positioned nucleosomes. We suggest that topological polymorphism of chromatin may play a role in transcription, with the {10n+5} fibers producing transcriptionally competent chromatin structures. This hypothesis is consistent with available data for yeast and, partially, for fly. We show that both fiber topoisomers (with ΔLk ≈ −1.5 and −1.0) have to be taken into account to interpret experimental data obtained using new techniques: genome-wide Micro-C, Hi-CO, and RICC-seq, as well as self-association of nucleosome arrays in vitro. The relative stability of these topoisomers is likely to depend on epigenetic histone modifications modulating the strength of internucleosome interactions. Potentially, our findings may reflect a general tendency of functionally distinct parts of the genome to retain topologically different higher-order structures.