ABSTRACT Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion. Using theoretical modelling and computer simulations we ask whether such diffusive extrusion could feasibly generate loops. Our simulations uncover an interesting ratchet effect (where an osmotic pressure promotes loop growth), and suggest, by comparison to recent in vitro and in vivo measurements, that diffusive extrusion can in principle generate loops of the size observed in the data. Extra View on : C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, and D. Marenduzzo “Non-equilibrium chromosome looping via molecular slip-links”, Physical Review Letters 119 138101 (2017)

中文翻译：

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没有马达的挤压：基因组组织环挤压模型的新观点

摘要染色质环挤出是形成 CTCF 环和拓扑域的流行模型。最近的 HiC 数据显示，强烈偏向于稳定环的 CTCF 结合基序的特定排列，而挤出是迄今为止唯一可以解释这一点的模型。然而，该模型需要一个马达来产生环，虽然 cohesin 是挤压因子的有力候选者，但尚未找到合适的马达蛋白（或 cohesin 本身的运动活性）。在这里，我们探索了一个新假设：没有运动，细胞核内的热运动会驱动挤压。使用理论建模和计算机模拟，我们询问这种扩散挤出是否可以可行地生成回路。我们的模拟揭示了一个有趣的棘轮效应（渗透压促进环路增长），并建议，通过与最近的体外和体内测量相比，扩散挤出原则上可以产生数据中观察到的大小的环。额外观点：CA Brackley、J. Johnson、D. Michieletto、AN Morozov、M. Nicodemi、PR Cook 和 D. Marenduzzo “通过分子滑动链接的非平衡染色体循环”，物理评论快报 119 138101（2017 年）