TY - JOUR
T1 - Stochastic effects of multiple regulators on expression profiles in eukaryotes
AU - Paszek, Pawel
AU - Lipniacki, Tomasz
AU - Brasier, Allan R.
AU - Tian, Bing
AU - Nowak, David E.
AU - Kimmel, Marek
N1 - Funding Information:
We would like to thank Dr. Bruce Luxon for discussion and support. This work was supported by NHLBI Contract N01-HV-28184, Proteomic technologies in airway inflammation (A. Kurosky, P.I.) and by KBN (Polish Committee for Scientific Research) Grant No. 8T07A 045 20.
PY - 2005/4/7
Y1 - 2005/4/7
N2 - 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-κB-dependent genes in HeLa cells. Our experimental data shows that NF-κB-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 beging 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.
AB - 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-κB-dependent genes in HeLa cells. Our experimental data shows that NF-κB-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 beging 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.
KW - Expression profiles
KW - NF-κB
KW - Single cell simulations
KW - Stochastic gene regulation
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U2 - 10.1016/j.jtbi.2004.10.023
DO - 10.1016/j.jtbi.2004.10.023
M3 - Article
C2 - 15652150
AN - SCOPUS:11844251994
SN - 0022-5193
VL - 233
SP - 423
EP - 433
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
IS - 3
ER -