Department of Chemistry, Stanford University, Stanford, California.
Department of Physics, University of Cambridge, Cambridge, United Kingdom.
Biophys J. 2020 Oct 20;119(8):1630-1639. doi: 10.1016/j.bpj.2020.08.039. Epub 2020 Sep 12.
We present a theoretical model that demonstrates the integral role chromosome organization and structural mechanics play in the spreading of histone modifications involved in epigenetic regulation. Our model shows that heterogeneous nucleosome positioning, and the resulting position-dependent mechanical properties, must be included to reproduce several qualitative features of experimental data of histone methylation spreading around an artificially induced "nucleation site." We show that our model recreates both the extent of spreading and the presence of a subdominant peak upstream of the transcription start site. Our model indicates that the spreading of epigenetic modifications is sensitive to heterogeneity in chromatin organization and the resulting variability in the chromatin's mechanical properties, suggesting that nucleosome spacing can directly control the conferral of epigenetic marks by modifying the structural mechanics of the chromosome. It further illustrates how the physical organization of the DNA polymer may play a significant role in re-establishing the epigenetic code upon cell division.
我们提出了一个理论模型，该模型证明了染色体组织和结构力学在涉及表观遗传调控的组蛋白修饰扩散中的整体作用。我们的模型表明，必须包括异质核小体定位以及由此产生的位置相关力学特性，才能重现组蛋白甲基化在人为诱导的“核化位点”周围扩散的实验数据的几个定性特征。我们表明，我们的模型再现了扩展的程度以及转录起始位点上游存在次要峰。我们的模型表明，表观遗传修饰的扩散对染色质组织的异质性以及染色质力学特性的可变性敏感，这表明核小体间隔可以通过改变染色体的结构力学直接控制表观遗传标记的赋予。它进一步说明了 DNA 聚合体的物理组织如何在细胞分裂后在重新建立表观遗传密码方面发挥重要作用。
