Signal Transduction Modeling And Data Analysis Of Eukaryotic Gene Transcriptional Bursting

With the advent of single-cell transcription detection technology,more and more researchers have found that during the study of transcription,the amount of RNA generated during the transcription process fluctuates greatly,the rate of RNA transcription is extremely unstable,and the generation time is extremely irregular.This highly random phenomenon is called transcription burst.Transcription burst occurs in the transcription of almost all eukaryotes.The complex multi-level regulation process involved in transcription makes the study of transcription burst extremely complicated,and the molecular mechanism behind them is not clear.Advanced single-cell detection technology has flaws in inspection resolution,which can easily cause two small bursts to be identified as one large transcription burst.This tricky problem complicates the theoretical study of transcription burst.In order to study the molecular mechanism of transcription burst,this paper combines the knowledge of probability theory,master equation,computer simulation and other knowledge to study the unsolved problems in the current transcription burst.The main results and contents completed are as follows:1.The unimodal and bimodal phenomena of actin 5 transcription initiation rate were studied.The gene model of actin 5 was established based on the general sequence of actin 5gene sequence and transcription.The unimodal and bimodal phenomena of actin initiation rate were reproduced in the experiment.The transcription kinetic parameters of actin 5including transcription burst frequency,transcription burst size,and transcription burst duration were calculated when the TATA box was normal and the TATA box was mutated.In addition,the situation where transcription initiation and transcription reinitiation was also studied before and after TATA mutation.Through the comparison of kinetic parameters,the transcription regulation mechanism of actin 5 was studied.2.Bypassing the shortcomings of single-cell technology resolution,two different methods for studying the mechanism of transcription burst regulation have been proposed.Based on the widely used two-state model,the fano factor and standard deviation were used to study the burst frequency modulation data and transcription burst size modulation data.It is shown that frequency modulation rather than size modulation is very consistent with experimental data from promoters of different genes.The information entropy of transcription regulation reinforces this conclusion.Furthermore,we show that data supporting size modulation can be explained by frequency modulation.Here,we propose two experimental resolution-independent methods to analyze the relationship between transcriptional regulation.The results show that burst frequency is only regulated by transcriptional activators,so data supporting size regulation can be reconciled by frequency regulation.