Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell Syst. 2017 Jan 25;4(1):97-108.e9. doi: 10.1016/j.cels.2016.11.012. Epub 2016 Dec 29.
Cells decide when, where, and to what level to express their genes by "computing" information from transcription factors (TFs) binding to regulatory DNA. How is the information contained in multiple TF-binding sites integrated to dictate the rate of transcription? The dominant conceptual and quantitative model is that TFs combinatorially recruit one another and RNA polymerase to the promoter by direct physical interactions. Here, we develop a quantitative framework to explore kinetic control, an alternative model in which combinatorial gene regulation can result from TFs working on different kinetic steps of the transcription cycle. Kinetic control can generate a wide range of analog and Boolean computations without requiring the input TFs to be simultaneously bound to regulatory DNA. We propose experiments that will illuminate the role of kinetic control in transcription and discuss implications for deciphering the cis-regulatory "code."
细胞通过“计算”转录因子（TFs）与调控 DNA 结合的信息，来决定何时、何地以及以何种水平表达其基因。那么，多个 TF 结合位点中包含的信息是如何整合起来决定转录速率的呢？目前占主导地位的概念和定量模型认为，TFs 通过直接的物理相互作用，组合地将彼此和 RNA 聚合酶募集到启动子上。在这里，我们开发了一个定量框架来探索动力学控制，这是一种替代模型，其中组合基因调控可以来自于在转录循环的不同动力学步骤上起作用的 TFs。动力学控制可以产生广泛的模拟和布尔计算，而不需要输入 TFs 同时与调控 DNA 结合。我们提出了一些实验方案，这些方案将阐明动力学控制在转录中的作用，并讨论其对破译顺式调控“密码”的影响。
