A Hill type equation can predict target gene expression driven by p53 pulsing

Hill 型方程可以预测由 p53 脉冲驱动的目标基因表达

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Abstract

Many factors determine target gene expression dynamics under p53 pulsing. In this study, I sought to determine the mechanism by which duration, frequency, binding affinity and maximal transcription rate affect the expression dynamics of target genes. Using an analytical method to solve a simple model, I found that the fold change of target gene expression increases relative to the number of p53 pulses, and the optimal frequency, 0.18 h(-1) , from two real p53 pulses drives the maximal fold change with a decay rate of 0.18 h(-1) . Moreover, p53 pulses may also lead to a higher fold change than sustained p53. Finally, I discovered that a Hill-type equation, including these effect factors, can characterise target gene expression. The average error between the theoretical predictions and experiments was 23%. Collectively, this equation advances the understanding of transcription factor dynamics, where duration and frequency play a significant role in the fine regulation of target gene expression with higher binding affinity.

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