Rosenfeld Nitzan, Alon Uri
Department of Molecular Cell Biology, Weizmann Institute of Science, 76100, Rehovot, Israel.
J Mol Biol. 2003 Jun 13;329(4):645-54. doi: 10.1016/s0022-2836(03)00506-0.
Sensory transcription networks generally control rapid and reversible gene expression responses to external stimuli. Developmental transcription networks carry out slow and irreversible temporal programs of gene expression during development. It is important to understand the design principles that underlie the structure of sensory and developmental transcription networks. Cascades, which are chains of regulatory reactions, are a basic structural element of transcription networks. When comparing databases of sensory and developmental transcription networks, a striking difference is found in the distribution of cascade lengths. Here, we suggest that delay times in the responses of the network present a design constraint that influences the network architecture. We experimentally studied the response times in simple cascades constructed of well-characterized repressors in Escherichia coli. Accurate kinetics at high temporal resolution was measured using green fluorescent protein (GFP) reporters. We find that transcription cascades can show long delays of about one cell-cycle time per cascade step. Mathematical analysis suggests that such a delay is characteristic of cascades that are designed to minimize the response times for both turning-on and turning-off gene expression. The need to achieve rapid reversible responses in sensory transcription networks may help explain the finding that long cascades are very rare in databases of E.coli and Saccharomyces cerevisiae sensory transcription networks. In contrast, long cascades are common in developmental transcription networks from sea urchin and from Drosophila melanogaster. Response delay constraints are likely to be less important for developmental networks, since they control irreversible processes on the timescale of cell-cycles. This study highlights a fundamental difference between the architecture of sensory and developmental transcription networks.
感觉转录网络通常控制对外部刺激的快速且可逆的基因表达反应。发育转录网络在发育过程中执行缓慢且不可逆的基因表达时间程序。理解感觉和发育转录网络结构背后的设计原则很重要。级联是调控反应链，是转录网络的基本结构元件。在比较感觉和发育转录网络的数据库时，发现级联长度的分布存在显著差异。在此，我们认为网络反应中的延迟时间呈现出一种影响网络架构的设计限制。我们通过实验研究了由大肠杆菌中特征明确的阻遏物构建的简单级联中的反应时间。使用绿色荧光蛋白（GFP）报告基因测量了高时间分辨率下的准确动力学。我们发现转录级联每级联步骤可能会显示约一个细胞周期时间的长延迟。数学分析表明，这种延迟是旨在使基因表达开启和关闭的反应时间最小化的级联的特征。在感觉转录网络中实现快速可逆反应的需求可能有助于解释在大肠杆菌和酿酒酵母感觉转录网络数据库中长级联非常罕见这一发现。相比之下，长级联在海胆和黑腹果蝇的发育转录网络中很常见。反应延迟限制对发育网络可能不太重要，因为它们在细胞周期的时间尺度上控制不可逆过程。这项研究突出了感觉和发育转录网络架构之间的根本差异。
