How to build a yeast nucleus
How to build a yeast nucleus
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如何构建酵母细胞核
作者：
Hua Wong;J. Arbona;C. Zimmer
包括基因表达和DNA修复在内的生物学功能受到基因组三维结构的影响，但其潜在的机制仍不清楚。值得注意的是，目前尚不清楚核结构在多大程度上是由聚合物的一般物理性质驱动的，还是由特定因素(如结合特定DNA序列的蛋白质)驱动的。用成像和生化技术对发芽酵母核进行了深入的研究，形成了大量关于基因座位置和DNA接触频率的定量数据集。我们最近描述了一个间期酵母核的定量模型，其中染色体被表示为被动移动的聚合链。这个模型忽略了DNA序列信息，除了着丝粒、端粒和核糖体DNA(RDNA)的特定限制。尽管该模型很简单，但它解释了绝大多数实验数据，包括绝对和相对基因座位置以及染色体和亚染色体尺度上的接触频率模式。这里，我们还说明了该模型再现染色质运动的观察特征的能力。我们的结果强烈表明，酵母核的动态大规模结构是由随机移动的聚合物的统计性质和一些序列特定的限制决定的，而不是由大量的DNA特定的因子或表观遗传修饰控制的。此外，我们的模型解释了最近测量到的同源重组效率的变化，说明了它在定量理解核结构的功能后果方面的潜力。
Biological functions including gene expression and DNA repair are affected by the 3D architecture of the genome, but the underlying mechanisms are still unknown. Notably, it remains unclear to what extent nuclear architecture is driven by generic physical properties of polymers or by specific factors such as proteins binding particular DNA sequences. The budding yeast nucleus has been intensely studied by imaging and biochemical techniques, resulting in a large quantitative data set on locus positions and DNA contact frequencies. We recently described a quantitative model of the interphase yeast nucleus in which chromosomes are represented as passively moving polymer chains. This model ignores the DNA sequence information except for specific constraints at the centromeres, telomeres, and the ribosomal DNA (rDNA). Despite its simplicity, the model accounts for a large majority of experimental data, including absolute and relative locus positions and contact frequency patterns at chromosomal and subchromosomal scales. Here, we also illustrate the model's ability to reproduce observed features of chromatin movements. Our results strongly suggest that the dynamic large-scale architecture of the yeast nucleus is dominated by statistical properties of randomly moving polymers with a few sequence-specific constraints, rather than by a large number of DNA-specific factors or epigenetic modifications. In addition, we show that our model accounts for recently measured variations in homologous recombination efficiency, illustrating its potential for quantitatively understanding functional consequences of nuclear architecture.