Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Mol Cell. 2009 Dec 11;36(5):894-9. doi: 10.1016/j.molcel.2009.11.018.
Many sensory systems (e.g., vision and hearing) show a response that is proportional to the fold-change in the stimulus relative to the background, a feature related to Weber's Law. Recent experiments suggest such a fold-change detection feature in signaling systems in cells: a response that depends on the fold-change in the input signal, and not on its absolute level. It is therefore of interest to find molecular mechanisms of gene regulation that can provide such fold-change detection. Here, we demonstrate theoretically that fold-change detection can be generated by one of the most common network motifs in transcription networks, the incoherent feedforward loop (I1-FFL), in which an activator regulates both a gene and a repressor of the gene. The fold-change detection feature of the I1-FFL applies to the entire shape of the response, including its amplitude and duration, and is valid for a wide range of biochemical parameters.
许多感觉系统(例如视觉和听觉)表现出的响应与刺激相对于背景的变化幅度成正比,这一特征与韦伯定律有关。最近的实验表明,细胞信号转导系统中存在这种变化幅度检测特征:响应取决于输入信号的变化幅度,而与其绝对水平无关。因此,寻找可以提供这种变化幅度检测的基因调控分子机制是很有意义的。在这里,我们从理论上证明,转录网络中最常见的网络基元之一——非相干前馈环(I1-FFL)可以产生这种变化幅度检测。在 I1-FFL 中,激活剂调节基因及其基因的抑制剂。I1-FFL 的变化幅度检测特征适用于响应的整个形状,包括其幅度和持续时间,并且在广泛的生化参数范围内有效。