论文标题
没有电动机的挤出:基因组组织的循环挤出模型的新摄
Extrusion without a motor: a new take on the loop extrusion model of genome organization
论文作者
论文摘要
染色质环挤出是形成CTCF环和拓扑结构域的流行模型。最近的HIC数据表明,有强烈的偏见,支持稳定环路的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。但是,该模型需要电动机生成环,尽管粘蛋白是挤出因子的强大候选者,但尚未找到合适的运动蛋白(或粘蛋白本身中的运动活性)。在这里,我们探讨了一个新的假设:没有电动机,核内的热运动驱动挤出。使用理论建模和计算机模拟,我们询问这种扩散的挤出是否可以可行地产生循环。我们的模拟发现了有趣的棘轮效应(渗透压促进环的生长),并与最近的体外和体内测量相比,建议扩散的挤压原则上可以生成数据中观察到的大小的环。 额外视图:C。A. Brackley,J。Johnson,D。Michieletto,A。N。Morozov,M。Nicodemi,P。R。Cook和D. Marenduzzo,“非平衡染色体染色体通过分子滑动链接进行循环”,物理评论信件,119,138101(2017)(2017)(2017年)(2017)
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)