Effects of elongation delay in transcription dynamics.

Xuan Zhang,Huiqin Jin,Zhuoqin Yang,Jinzhi Lei

doi:10.3934/mbe.2014.11.1431

Xuan Zhang, Huiqin Jin + Show 2 more

Open Access

https://doi.org/10.3934/mbe.2014.11.1431

Copy DOI

Abstract

In the transcription process, elongation delay is induced by the movement of RNA polymerases (RNAP) along the DNA sequence, and can result in changes in the transcription dynamics. This paper studies the transcription dynamics that involved the elongation delay and effects of cell division and DNA replication. The stochastic process of gene expression is modeled with delay chemical master equation with periodic coefficients, and is studied numerically through the stochastic simulation algorithm with delay. We show that the average transcription level approaches to a periodic dynamics over cell cycles at homeostasis, and the elongation delay can reduce the transcription level and increase the transcription noise. Moreover, the transcription elongation can induce bimodal distribution of mRNA levels that can be measured by the techniques of flow cytometry.

Highlights

Transcription is the first step of gene expression, through which genetic information encoded in DNA is transcribed to mRNA by RNA polymerases (RNAP)
When applying flow cytometry to explore stochastic gene expression, we ask how transcriptional controls can affect the distributions of RNA and protein levels, whether different types of cell-to-cell variability can be induced by changing the transcription elongation, and how the RNA distributions depend on the chemical reaction rates? To answer these questions with our discrete model, we randomly chose control parameters and for each set of the parameters we numerically investigated the resulting distribution of RNA from a group of cells
We have studied the transcription dynamics with elongation delay through chemical master equation and stochastic simulation with delay

Summary

Introduction

Transcription is the first step of gene expression, through which genetic information encoded in DNA is transcribed to mRNA by RNA polymerases (RNAP). The elongation delays significantly contribute to the timing mechanisms during development [45], and is tightly controlled by the rate of translation [32] Such a cooperation mechanism ensures that transcription is always adjusted to translational needs at different genes and under various growth conditions [32]. Ribeiro studied a delayed stochastic model of transcription at single nucleotide level that includes the promoter complex formation, pausing, arresting, disincorporation and editing, pyrophosphorolysis, and premature termination [34, 37]. Simulations based on their model showed that mRNA production exhibits bursting and pulses dynamics, and the elongation dynamics can shape the bursting transcription [11, 34]. Long elongation delay can induce bimodal distributions in RNA numbers even for a constitutive expression gene, and provides a novel mechanism of having bimodal distribution in gene expression

Model and methods

Results

Discussion