Parmar Jyotsana J, Das Dibyendu, Padinhateeri Ranjith
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India
Department of Physics, Indian Institute of Technology Bombay, Mumbai 400076, India
Nucleic Acids Res. 2016 Feb 29;44(4):1630-41. doi: 10.1093/nar/gkv1153. Epub 2015 Nov 8.
It is being increasingly realized that nucleosome organization on DNA crucially regulates DNA-protein interactions and the resulting gene expression. While the spatial character of the nucleosome positioning on DNA has been experimentally and theoretically studied extensively, the temporal character is poorly understood. Accounting for ATPase activity and DNA-sequence effects on nucleosome kinetics, we develop a theoretical method to estimate the time of continuous exposure of binding sites of non-histone proteins (e.g. transcription factors and TATA binding proteins) along any genome. Applying the method to Saccharomyces cerevisiae, we show that the exposure timescales are determined by cooperative dynamics of multiple nucleosomes, and their behavior is often different from expectations based on static nucleosome occupancy. Examining exposure times in the promoters of GAL1 and PHO5, we show that our theoretical predictions are consistent with known experiments. We apply our method genome-wide and discover huge gene-to-gene variability of mean exposure times of TATA boxes and patches adjacent to TSS (+1 nucleosome region); the resulting timescale distributions have non-exponential tails.
人们越来越认识到,DNA上的核小体组织对DNA-蛋白质相互作用以及由此产生的基因表达起着至关重要的调节作用。虽然已经对DNA上核小体定位的空间特征进行了广泛的实验和理论研究,但对其时间特征却知之甚少。考虑到ATP酶活性和DNA序列对核小体动力学的影响,我们开发了一种理论方法来估计非组蛋白(如转录因子和TATA结合蛋白)结合位点在任何基因组上的连续暴露时间。将该方法应用于酿酒酵母,我们发现暴露时间尺度由多个核小体的协同动力学决定,其行为往往与基于静态核小体占有率的预期不同。通过研究GAL1和PHO5启动子中的暴露时间,我们表明我们的理论预测与已知实验一致。我们在全基因组范围内应用我们的方法,发现TATA框和与转录起始位点相邻的区域(+1核小体区域)的平均暴露时间在基因间存在巨大差异;由此产生的时间尺度分布具有非指数尾部。