School of Physics, Georgia Institute of Technology, Atlanta, Georgia, USA.
PLoS One. 2013 May 20;8(5):e63072. doi: 10.1371/journal.pone.0063072. Print 2013.
Nucleosomes, which are the basic packaging units of chromatin, are stably positioned in promoters upstream of most stress-inducible genes. These promoter nucleosomes are generally thought to repress gene expression due to exclusion; they prevent transcription factors from accessing their target sites on the DNA. However, the role of promoter nucleosomes that do not directly occlude transcription factor binding sites is not obvious. Here, we varied the stability of a non-occluding nucleosome positioned between a transcription factor binding site and the TATA box region in an inducible yeast promoter and measured downstream gene expression level. We found that gene expression level depends on the occupancy of the non-occluding nucleosome in a non-monotonic manner. We postulated that a non-occluding nucleosome can serve both as a vehicle of and a barrier to chromatin remodeling activity and built a quantitative, nonequilibrium model to explain the observed nontrivial effect of the intervening nucleosome. Our work sheds light on the dual role of nucleosome as a repressor and an activator and expands the standard model of gene expression to include irreversible promoter chromatin transitions.
核小体是染色质的基本包装单位，它们稳定地定位于大多数诱导应激基因的启动子上游。这些启动子核小体通常被认为由于排斥而抑制基因表达；它们阻止转录因子访问 DNA 上的靶位点。然而，对于不直接阻碍转录因子结合位点的启动子核小体的作用并不明显。在这里，我们改变了位于诱导酵母启动子中转录因子结合位点和 TATA 盒区域之间的非阻碍核小体的稳定性，并测量了下游基因表达水平。我们发现基因表达水平与非阻碍核小体的占据呈非单调关系。我们假设，非阻碍核小体可以作为染色质重塑活性的载体和障碍，并构建了一个定量的、非平衡模型来解释观察到的中间核小体的非平凡效应。我们的工作揭示了核小体作为抑制剂和激活剂的双重作用，并将基因表达的标准模型扩展到包括不可逆的启动子染色质转变。
