The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes.
The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes.
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间隔排列的核小体与染色质浓缩和基因沉默直接相关。ATP依赖性染色质组装因子（ACF）在体外形成这样的结构，并且是体内沉默所需的。ACF通过使核小体比较短侧翼DNA更快地朝向较长侧翼DNA不断移动来产生并维持核小体间距。但是这种酶是如何在核小体的两侧快速来回移动以实现双向运动的还不清楚。我们发现，核小体运动依赖于两个ACF分子的合作，这表明ACF的功能作为ATP酶的二聚体。此外，核苷酸状态决定二聚体是否紧密接合核小体的一侧还是两侧。三维重建的ATP酶-核小体复合物在一个激活的ATP状态的单粒子电子显微镜揭示了一个二聚体的架构，其中两个ATP酶面对对方。我们的研究结果提出了一个模型，其中两个ATP酶以协调的方式工作，轮流从事核小体的任何一侧，从而允许进行性双向运动。这种新的二聚体马达机制不同于二聚体马达，如驱动蛋白和二聚体解旋酶，其产生单向易位，并反映了移动核小体的马达所面临的独特挑战。
Evenly spaced nucleosomes directly correlate with condensed chromatin and gene silencing. The ATP-dependent chromatin assembly factor (ACF) forms such structures in vitro and is required for silencing in vivo. ACF generates and maintains nucleosome spacing by constantly moving a nucleosome towards the longer flanking DNA faster than the shorter flanking DNA. But how the enzyme rapidly moves back and forth between both sides of a nucleosome to accomplish bidirectional movement is unknown. We show that nucleosome movement depends cooperatively on two ACF molecules, suggesting that ACF functions as a dimer of ATPases. Further, the nucleotide state determines whether the dimer closely engages one vs. both sides of the nucleosome. Three-dimensional reconstruction by single particle electron microscopy of the ATPase-nucleosome complex in an activated ATP state reveals a dimer architecture in which the two ATPases face each other. Our results suggest a model in which the two ATPases work in a coordinated manner, taking turns to engage either side of a nucleosome, thereby allowing processive bidirectional movement. This novel dimeric motor mechanism differs from that of dimeric motors such as kinesin and dimeric helicases that processively translocate unidirectionally and reflects the unique challenges faced by motors that move nucleosomes.
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