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

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 mode...

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Detalles Bibliográficos
Autor principal: Shi, Xiaomin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167869/
https://www.ncbi.nlm.nih.gov/pubmed/33955710
http://dx.doi.org/10.1002/2211-5463.13179
Descripción
Sumario: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.