Modeling of Hysteresis in a Mammalian Gene Regulatory Network

Hysteresis, observed in cell cycle or gene regulatory network experimentally, has a pivotal impact on biological systems, in the sense of enabling cells to adopt multiple internal expression states in response to a single external input signal. In a synthetic hysteretic mammalian transcription network, the transactivator (TA) cotranscribed by TA’s cognate promoter is repressed by the transrepressor, whose activity is modulated by the macrolide antibiotic erythromycin (EM). The SEAP (human placental secreted alkaline phosphatase) is expressed cocistronically with TA. The interconnection of SEAP concentrations versus EM concentrations is demonstrated to be hysteresis in the experiment. In this paper, the modified Bouc-Wen hysteresis model is developed to describe the hysteresis in the mammalian gene network. Simulation result is presented to verify the capability and accuracy of the mathematical model to describe the hysteresis phenomenon in the mammalian gene regulatory network. Comparative study has shown better performance with this model than previous one in the literature.