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Designing sequential transcription logic: a simple genetic circuit for conditional memory

机译:设计顺序转录逻辑:用于条件记忆的简单遗传电路

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摘要

The ability to learn and respond to recurrent events depends on the capacity to remember transient biological signals received in the past. Moreover, it may be desirable to remember or ignore these transient signals conditioned upon other signals that are active at specific points in time or in unique environments. Here, we propose a simple genetic circuit in bacteria that is capable of conditionally memorizing a signal in the form of a transcription factor concentration. The circuit behaves similarly to a “data latch” in an electronic circuit, i.e. it reads and stores an input signal only when conditioned to do so by a “read command.” Our circuit is of the same size as the well-known genetic toggle switch (an unconditional latch) which consists of two mutually repressing genes, but is complemented with a “regulatory front end” involving protein heterodimerization as a simple way to implement conditional control. Deterministic and stochastic analysis of the circuit dynamics indicate that an experimental implementation is feasible based on well-characterized genes and proteins. It is not known, to which extent molecular networks are able to conditionally store information in natural contexts for bacteria. However, our results suggest that such sequential logic elements may be readily implemented by cells through the combination of existing protein–protein interactions and simple transcriptional regulation.Electronic Supplementary MaterialThe online version of this article (doi:10.1007/s11693-007-9006-8) contains supplementary material, which is available to authorized users.
机译:学习和应对复发事件的能力取决于记忆过去收到的瞬时生物信号的能力。此外,可能希望记住或忽略以在特定时间点或在独特环境中处于活动状态的其他信号为条件的这些瞬态信号。在这里,我们提出了一种细菌中的简单遗传回路,该回路能够有条件地记忆转录因子浓度形式的信号。该电路的行为类似于电子电路中的“数据锁存器”,即,只有在以“读取命令”为条件的情况下,才读取并存储输入信号。我们的电路与众所周知的遗传拨动开关(无条件锁存器)的大小相同,后者由两个相互抑制的基因组成,但通过涉及蛋白质异二聚化的“调节前端”作为实现条件控制的简单方法进行了补充。对电路动力学的确定性和随机性分析表明,基于特征明确的基因和蛋白质,实验实现是可行的。尚不知道分子网络在何种程度上能够在细菌的自然环境中有条件地存储信息。但是,我们的研究结果表明,通过结合现有的蛋白质间相互作用和简单的转录调控,细胞可以很容易地实现这种顺序逻辑元件。电子补充材料本文的在线版本(doi:10.1007 / s11693-007-9006-8 )包含补充材料,授权用户可以使用。

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