Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina.
Instituto de Física de Buenos Aires (IFIBA), CONICET-UBA, Buenos Aires, C1428EGA, Argentina.
Sci Rep. 2023 Feb 14;13(1):2652. doi: 10.1038/s41598-023-29539-3.
Cells detect changes in their environment and generate responses, often involving changes in gene expression. In this paper we use information theory and a simple transcription model to analyze whether the resulting gene expression serves to identify extracellular stimuli and assess their intensity when they are encoded in the amplitude, duration or frequency of pulses of a transcription factor's nuclear concentration (or activation state). We find, for all cases, that about three ranges of input strengths can be distinguished and that maximum information transmission occurs for fast and high activation threshold promoters. The three input modulation modes differ in the sensitivity to changes in the promoters parameters. Frequency modulation is the most sensitive and duration modulation, the least. This is key for signal identification: there are promoter parameters that yield a relatively high information transmission for duration or amplitude modulation and a much smaller value for frequency modulation. The reverse situation cannot be found with a single promoter transcription model. Thus, pulses of transcription factors can selectively activate the "frequency-tuned" promoter while prolonged nuclear accumulation would activate promoters of all three modes simultaneously. Frequency modulation is therefore highly selective and better suited than the other encoding modes for signal identification without requiring other mediators of the transduction process.
细胞检测其环境变化，并生成响应，通常涉及基因表达的变化。在本文中，我们使用信息论和一个简单的转录模型来分析，当细胞将细胞外刺激的编码为转录因子核浓度（或激活状态）脉冲的幅度、持续时间或频率时，所产生的基因表达是否有助于识别这些刺激并评估其强度。我们发现，对于所有情况，大约可以区分三个输入强度范围，并且对于快速和高激活阈值启动子，最大信息传输发生。三种输入调制模式在对启动子参数变化的敏感性方面有所不同。频率调制最敏感，持续时间调制最不敏感。这对于信号识别至关重要：存在一些启动子参数，对于持续时间或幅度调制，其信息传输相对较高，而对于频率调制，则值较小。对于单个启动子转录模型，不能找到相反的情况。因此，转录因子的脉冲可以选择性地激活“频率调谐”启动子，而核积累的延长将同时激活三种模式的启动子。因此，频率调制具有高度选择性，比其他编码模式更适合于信号识别，而无需信号转导过程中的其他介质。
