Stochastic effects of multiple regulators on expression profiles in eukaryotes.
The stochastic nature of gene regulation still remains not fully understood. In eukaryotes, the stochastic effects are primarily attributable to the binary nature of genes, which are considered either switched "on" or "off" due to the action of the transcription factors binding to the promoter. In the time period when the gene is activated, bursts of mRNA transcript are produced. In the present paper, we investigate regulation of gene expression at the single cell level. We propose a mechanism of gene regulation, which is able to explain the observed distinct transcription profiles assuming the number of co-regulatory activities, without attempting to identify the specific proteins involved. The model is motivated by our experiments on NF-kappaB-dependent genes in HeLa cells. Our experimental data shows that NF-kappaB-dependent genes can be stratified into three characteristic groups according to their expression profiles: early, intermediate and late having maximum of expression at about 1, 3 and 6 h, respectively, from the beginning of TNF stimulation. We provide a tractable analytical approach, not only in the terms of expected expression profiles and their moments, which corresponds to the measurements on the cell population, but also in the terms of single cell behavior. Comparison between these two modes of description reveals that single cells behave qualitatively different from the cell population. This analysis provides insights useful for understanding of microarray experiments.
Paszek
Pawel
P
Department of Statistics, Rice University, 6100 Main Street, MS-138, Houston, TX 77005, USA. ppaszek@rice.edu
Lipniacki
Tomasz
T
Brasier
Allan R
AR
Tian
Bing
B
Nowak
David E
DE
Kimmel
Marek
M
D000818:Animals; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing; D008957:Models, Genetic; D014158:Transcription, Genetic