Cell cycle-specified fluctuation of nucleosome occupancy at gene promoters.
Cell cycle-specified fluctuation of nucleosome occupancy at gene promoters.
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DOI：
10.1371/journal.pgen.0020158
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发表时间：
2006-09-22
期刊：
影响因子：
4.5
通讯作者：
Lieb JD
中科院分区：
文献类型：
--
作者：
Hogan GJ;Lee CK;Lieb JD
将DNA包装成核小体会影响潜在调控信息的可及性。核小体的占据和定位在出芽酵母（Saccharomyces cerevisiae）中得到了最好的表征，尽管是在异步细胞群体中或在PHO5和GAL1-10等单个启动子上。利用FAIRE（甲醛辅助分离调控元件）和全基因组微阵列技术，研究了酿酒酵母同步种群在整个有丝分裂细胞周期中核小体占用率的变化。也许令人惊讶的是，核小体占用率在细胞周期阶段之间没有表现出大的全局变化。然而，核小体在细胞周期调控基因启动子上的占用率在细胞周期阶段特异性降低，在细胞周期阶段该基因表现出峰值表达，s期基因明显例外。我们提出的数据，建立FAIRE作为一个高通量的方法来分析核小体占用。在任何系统中，首次在整个细胞周期中绘制全基因组核小体占用率。大多数细胞周期调控基因启动子核小体占用率的波动提供了独立的证据，表明这些基因的周期性表达主要受转录水平的控制。G2/M基因的启动子与其他细胞周期启动子的区别在于，在整个细胞周期中，核小体的基线占用率异常低。这一观察结果，再加上整个细胞周期中编码位点和非编码位点之间的核小体占用状态的维持，表明核小体占用变化的最大组成部分是“硬连线”，可能在DNA序列水平上。每个细胞都含有基因组的完整拷贝，基因组由DNA组成。为了使基因组嵌入细胞核，DNA链被缠绕在由组蛋白组成的线轴上。通过包装DNA，组蛋白还控制对DNA的访问，从而影响基因的开启和关闭时间。作者提出了两个主要发现。首先，他们展示了一种新的、简单的方法来确定基因缠绕在组蛋白上的紧密程度。其次，他们使用新方法来确定在细胞生长和分裂的一个周期中，每个基因的DNA包装发生了什么变化。他们发现，当基因在整个细胞周期中被打开时，控制这些基因的DNA包装变得松散，当基因被关闭时，它又变得紧密。然而，一些细胞周期调节基因不符合这种模式，这表明这些基因有另一种调节方式。有趣的是，单个基因的细胞周期相关的包装差异小于不同基因组之间明显的包装差异。这表明，DNA包装方式的大部分差异可能是由DNA序列本身控制的，其他因素的影响较小。
The packaging of DNA into nucleosomes influences the accessibility of underlying regulatory information. Nucleosome occupancy and positioning are best characterized in the budding yeast Saccharomyces cerevisiae, albeit in asynchronous cell populations or on individual promoters such as PHO5 and GAL1–10. Using FAIRE (formaldehyde-assisted isolation of regulatory elements) and whole-genome microarrays, we examined changes in nucleosome occupancy throughout the mitotic cell cycle in synchronized populations of S. cerevisiae. Perhaps surprisingly, nucleosome occupancy did not exhibit large, global variation between cell cycle phases. However, nucleosome occupancy at the promoters of cell cycle–regulated genes was reduced specifically at the cell cycle phase in which that gene exhibited peak expression, with the notable exception of S-phase genes. We present data that establish FAIRE as a high-throughput method for assaying nucleosome occupancy. For the first time in any system, nucleosome occupancy was mapped genome-wide throughout the cell cycle. Fluctuation of nucleosome occupancy at promoters of most cell cycle–regulated genes provides independent evidence that periodic expression of these genes is controlled mainly at the level of transcription. The promoters of G2/M genes are distinguished from other cell cycle promoters by an unusually low baseline nucleosome occupancy throughout the cell cycle. This observation, coupled with the maintenance throughout the cell cycle of the stereotypic nucleosome occupancy states between coding and non-coding loci, suggests that the largest component of variation in nucleosome occupancy is “hard wired,” perhaps at the level of DNA sequence. Every cell contains a complete copy of the genome, which is comprised of DNA. To fit the genome into the cell nucleus, DNA strands are wound around spools made of proteins called histones. By packing DNA, histones also control access to DNA, which influences when genes can be turned on and off. The authors present two main findings. First, they demonstrate a new, simple method to determine how tightly genes are wrapped around histones. Second, they use the new method to determine what happens to DNA packaging at every gene through one cycle of cell growth and division. They find that as genes get turned on throughout the cell cycle, the packaging of DNA that controls those genes becomes loose, and as genes get turned off, it becomes tight again. However, some cell cycle–regulated genes do not fit this pattern, suggesting another means of regulation for these genes. Interestingly, cell cycle–related differences in packaging at single genes are smaller than differences in packaging that are always apparent between different groups of genes. This suggests that most differences in how DNA is packaged may be controlled by the sequence of DNA itself, with smaller contributions from other factors.
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