具有表观遗传重着色的Polymer模型揭示了染色质结构域从头建立和3D组织的途径
A Polymer Model with Epigenetic Recolouring Reveals a Pathway for the de novo Establishment and 3D Organisation of Chromatin Domains
摘要：
发育中最重要的问题之一是表观遗传域如何在细胞内首先建立，然后维持。为了解决这个问题，我们提出了一个框架，耦合3D染色质折叠动力学，一个“仿形”过程建模的写作表观遗传标记。由于许多染色质内的相互作用是由桥接蛋白介导的，我们认为一个“双态”模型与两个表观遗传标记是相似的（无论是活跃或不活跃）之间的自吸引的相互作用。该模型显示了一个一阶样的过渡之间的肿胀，表观遗传紊乱，相，和一个紧凑的，表观遗传连贯，染色质球。如果自吸引强度超过阈值，染色质动力学就会变成玻璃状，相应的相互作用网络就会冻结。通过修改表观遗传的读写过程，根据更多的生物学启发的假设，我们的聚合物模型与concurrenting概括了超灵敏的反应表观遗传开关的扰动，并占多域构象，惊人地相似的拓扑关联域中观察到的真核染色体。
英文摘要：
One of the most important problems in development is how epigenetic domains can be first established, and then maintained, within cells. To address this question, we propose a framework which couples 3D chromatin folding dynamics, to a "recolouring" process modelling the writing of epigenetic marks. Because many intra-chromatin interactions are mediated by bridging proteins, we consider a "two-state" model with self-attractive interactions between two epigenetic marks which are alike (either active or inactive). This model displays a first-order-like transition between a swollen, epigenetically disordered, phase, and a compact, epigenetically coherent, chromatin globule. If the self-attraction strength exceeds a threshold, the chromatin dynamics becomes glassy, and the corresponding interaction network freezes. By modifying the epigenetic read-write process according to more biologically-inspired assumptions, our polymer model with recolouring recapitulates the ultrasensitive response of epigenetic switches to perturbations, and accounts for multi-domain conformations, strikingly similar to the topologically-associating-domains observed in eukaryotic chromosomes.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
