Biophysics Unit (CSIC-UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain.
Nucleic Acids Res. 2011 Sep 1;39(16):6854-63. doi: 10.1093/nar/gkr272. Epub 2011 May 20.
Numerous transcription factors self-assemble into different order oligomeric species in a way that is actively regulated by the cell. Until now, no general functional role has been identified for this widespread process. Here, we capture the effects of modulated self-assembly in gene expression with a novel quantitative framework. We show that this mechanism provides precision and flexibility, two seemingly antagonistic properties, to the sensing of diverse cellular signals by systems that share common elements present in transcription factors like p53, NF-κB, STATs, Oct and RXR. Applied to the nuclear hormone receptor RXR, this framework accurately reproduces a broad range of classical, previously unexplained, sets of gene expression data and corroborates the existence of a precise functional regime with flexible properties that can be controlled both at a genome-wide scale and at the individual promoter level.
许多转录因子以一种被细胞主动调控的方式自组装成不同的有序寡聚体。到目前为止，还没有确定这个广泛存在的过程的一般功能作用。在这里，我们用一种新的定量框架捕捉到了调节自组装对基因表达的影响。我们表明，这种机制为通过共享转录因子（如 p53、NF-κB、STATs、Oct 和 RXR 中存在的共同元件的系统）感知不同的细胞信号提供了精度和灵活性，这两个看似对立的特性。将该框架应用于核激素受体 RXR，它可以准确地再现广泛的经典的、以前无法解释的基因表达数据集，并证实了存在一个具有灵活特性的精确功能范围，这种特性可以在全基因组范围和单个启动子水平上进行控制。
