SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Road, Edinburgh, EH9 3FD, UK.
Soft Matter. 2020 Mar 4;16(9):2406-2414. doi: 10.1039/c9sm01875a.
We use Brownian dynamics simulations to study the formation of chromatin loops through diffusive sliding of slip-link-like proteins, mimicking the behaviour of cohesin molecules. We recently proposed that diffusive sliding is sufficient to explain the extrusion of chromatin loops of hundreds of kilo-base-pairs (kbp), which may then be stabilised by interactions between cohesin and CTCF proteins. Here we show that the flexibility of the chromatin fibre strongly affects this dynamical process, and find that diffusive loop extrusion is more efficient on stiffer chromatin regions. We also show that the dynamics of loop formation are faster in confined and collapsed chromatin conformations but that this enhancement is counteracted by the increased crowding. We provide a simple theoretical argument explaining why stiffness and collapsed conformations favour diffusive extrusion. In light of the heterogeneous physical and conformational properties of eukaryotic chromatin, we suggest that our results are relevant to understand the looping and organisation of interphase chromosomes in vivo.
我们使用布朗动力学模拟来研究通过类似滑链蛋白的扩散滑动形成染色质环，模拟黏合蛋白分子的行为。我们最近提出，扩散滑动足以解释数百千碱基对（kbp）的染色质环的挤出，然后通过黏合蛋白和 CTCF 蛋白之间的相互作用稳定这些环。在这里，我们表明染色质纤维的柔韧性强烈影响这个动态过程，并发现扩散环挤出在更刚性的染色质区域更有效。我们还表明，在受限和塌陷的染色质构象中，环形成的动力学更快，但这种增强作用被增加的拥挤所抵消。我们提供了一个简单的理论论证，解释了为什么刚性和塌陷构象有利于扩散挤出。鉴于真核染色质的异质物理和构象特性，我们认为我们的结果与理解体内有丝分裂染色体的环化和组织有关。
