EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, United Kingdom.
Genome Res. 2012 Jan;22(1):84-94. doi: 10.1101/gr.124099.111. Epub 2011 Sep 19.
Nucleosomes play an important role in gene regulation. Molecular studies observed that nucleosome binding in promoters tends to be repressive. In contrast, genomic studies have delivered conflicting results: An analysis of yeast grown on diverse carbon sources reported that nucleosome occupancies remain largely unchanged between conditions, whereas a study of the heat-shock response suggested that nucleosomes get evicted at promoters of genes with increased expression. Consequently, there are few general principles that capture the relationship between chromatin organization and transcriptional regulation. Here, we present a qualitative model for nucleosome positioning in Saccharomyces cerevisiae that helps explain important properties of gene expression. By integrating publicly available data sets, we observe that promoter-bound nucleosomes assume one of four discrete configurations that determine the active and silent transcriptional states of a gene, but not its expression level. In TATA-box-containing promoters, nucleosome architecture indicates the amount of transcriptional noise. We show that >20% of genes switch promoter states upon changes in cellular conditions. The data suggest that DNA-binding transcription factors together with chromatin-remodeling enzymes are primarily responsible for the nucleosome architecture. Our model for promoter nucleosome architecture reconciles genome-scale findings with molecular studies; in doing so, we establish principles for nucleosome positioning and gene expression that apply not only to individual genes, but across the entire genome. The study provides a stepping stone for future models of transcriptional regulation that encompass the intricate interplay between cis- and trans-acting factors, chromatin, and the core transcriptional machinery.
核小体在基因调控中发挥着重要作用。分子研究观察到，启动子中的核小体结合往往具有抑制作用。相比之下，基因组研究却给出了相互矛盾的结果：一项关于在不同碳源上生长的酵母的分析报告称，在不同条件下，核小体的占有率基本保持不变，而对热休克反应的研究表明，在表达增加的基因的启动子处，核小体被逐出。因此，很少有一般性的原则能够捕捉到染色质结构与转录调控之间的关系。在这里，我们提出了一种酿酒酵母核小体定位的定性模型，有助于解释基因表达的重要性质。通过整合公开的数据集，我们观察到，结合在启动子上的核小体呈现出四种离散的构象之一，这四种构象决定了一个基因的活跃和沉默转录状态，但不决定其表达水平。在包含 TATA 盒的启动子中，核小体结构决定了转录噪声的数量。我们表明，>20%的基因在细胞条件发生变化时会改变启动子状态。这些数据表明，DNA 结合转录因子和染色质重塑酶主要负责核小体的结构。我们的启动子核小体结构模型将全基因组研究结果与分子研究结果统一起来；这样做的同时，我们建立了核小体定位和基因表达的原则，这些原则不仅适用于单个基因，也适用于整个基因组。该研究为未来的转录调控模型提供了一个垫脚石，这些模型涵盖了顺式和反式作用因子、染色质和核心转录机器之间复杂的相互作用。
