title: Differential transcriptional regulation by alternatively designed mechanisms: A mathematical modeling approach.
abstract: Cells maintain cellular homeostasis employing different regulatory mechanisms to respond external stimuli. We study two groups of signal-dependent transcriptional regulatory mechanisms. In the first group, we assume that repressor and activator proteins compete for binding to the same regulatory site on DNA (competitive mechanisms). In the second group, they can bind to different regulatory regions in a noncompetitive fashion (noncompetitive mechanisms). For both competitive and noncompetitive mechanisms, we studied the gene expression dynamics by increasing the repressor or decreasing the activator abundance (inhibition mechanisms), or by decreasing the repressor or increasing the activator abundance (activation mechanisms). We employed delay differential equation models. Our simulation results show that the competitive and noncompetitive inhibition mechanisms exhibit comparable repression effectiveness. However, response time is fastest in the noncompetitive inhibition mechanism due to increased repressor abundance, and slowest in the competitive inhibition mechanism by increased repressor level. The competitive and noncompetitive inhibition mechanisms through decreased activator abundance show comparable and moderate response times, while the competitive and noncompetitive activation mechanisms by increased activator protein level display more effective and faster response. Our study exemplifies the importance of mathematical modeling and computer simulation in the analysis of gene expression dynamics.
authors: Division of Natural Sciences, New College of Florida, Bayshore Road, Sarasota, FL, USA.
authors: Necmettin
authors: N
authors: Yildirim
authors: Department of Mathematics, Florida State University, W College Ave, Tallahassee, FL, USA.
authors: Mehmet Emin
authors: ME
authors: Aktas
authors: Department of Mathematics, North Carolina State University, Raleigh, NC, USA.
authors: Seyma Nur
authors: SN
authors: Ozcan
authors: Department of Computer Science, Florida State University, W College Ave, Tallahassee, FL, USA.
authors: Esra
authors: E
authors: Akbas
authors: Departments of Biology and Mathematics, Colgate University, Oak Drive, Hamilton, NY, USA.
authors: Ahmet
authors: A
authors: Ay
mesh_terms: D003198:Computer Simulation; D005786:Gene Expression Regulation; D008954:Models, Biological; D008962:Models, Theoretical
keywords: Mathematical modeling; delayed differential equation; gene regulation; gene regulatory network; numerical simulation; signal transduction