Department of Biosciences and Bioengineering and Wadhwani Research Centre for Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
Proc Natl Acad Sci U S A. 2011 May 10;108(19):7799-803. doi: 10.1073/pnas.1015206108. Epub 2011 Apr 25.
Accounting for enzyme-mediated active sliding, disassembly, and sequence-dependent positioning of nucleosomes, we simulate nucleosome occupancy over cell-cycle-scale times using a stochastic kinetic model. We show that ATP-dependent active nucleosome sliding and nucleosome removal processes are essential to obtain in vivo-like nucleosome positioning. While active sliding leads to dense nucleosome filling, sliding events alone cannot ensure sequence-dependent nucleosome positioning: Active nucleosome removal is the crucial remodeling event that drives positioning. We also show that remodeling activity changes nucleosome dynamics from glassy to liquid-like, and that remodeling dramatically influences exposure dynamics of promoter regions.
考虑到酶介导的活性滑动、解组装以及核小体的序列依赖性定位,我们使用随机动力学模型模拟了细胞周期尺度上的核小体占有率。结果表明,ATP 依赖性的活性核小体滑动和核小体去除过程对于获得类似于体内的核小体定位是必不可少的。虽然活性滑动导致核小体紧密填充,但单独的滑动事件并不能确保序列依赖性的核小体定位:活性核小体去除是驱动定位的关键重塑事件。我们还表明,重塑活性使核小体动力学从玻璃态转变为液态样,并且重塑极大地影响了启动子区域的暴露动力学。