Pollak Yaroslav, Goldberg Sarah, Amit Roee
Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa, Israel.
PLoS Comput Biol. 2017 Jan 13;13(1):e1005337. doi: 10.1371/journal.pcbi.1005337. eCollection 2017 Jan.
We model the regulatory role of proteins bound to looped DNA using a simulation in which dsDNA is represented as a self-avoiding chain, and proteins as spherical protrusions. We simulate long self-avoiding chains using a sequential importance sampling Monte-Carlo algorithm, and compute the probabilities for chain looping with and without a protrusion. We find that a protrusion near one of the chain's termini reduces the probability of looping, even for chains much longer than the protrusion-chain-terminus distance. This effect increases with protrusion size, and decreases with protrusion-terminus distance. The reduced probability of looping can be explained via an eclipse-like model, which provides a novel inhibitory mechanism. We test the eclipse model on two possible transcription-factor occupancy states of the D. melanogaster eve 3/7 enhancer, and show that it provides a possible explanation for the experimentally-observed eve stripe 3 and 7 expression patterns.
我们通过模拟来构建与环状DNA结合的蛋白质的调控作用，在该模拟中，双链DNA被表示为自回避链，蛋白质被表示为球形突出物。我们使用顺序重要性抽样蒙特卡罗算法模拟长自回避链，并计算有和没有突出物时链环化的概率。我们发现，即使对于比突出物 - 链末端距离长得多的链，靠近链末端之一的突出物也会降低环化的概率。这种效应随着突出物大小的增加而增加，随着突出物 - 末端距离的增加而减小。环化概率的降低可以通过类似日食的模型来解释，该模型提供了一种新的抑制机制。我们在黑腹果蝇eve 3/7增强子的两种可能的转录因子占据状态上测试了日食模型，并表明它为实验观察到的eve条纹3和7的表达模式提供了一种可能的解释。
