A Steady State Model for the Transcriptional Regulation of Filamentous Growth in Saccharomyces cerevisiae

Article type: Research Article

Authors: Unni Vinod, Palakkad Krishnan | Venkatesh, Kareenhalli V.^;

Affiliations: School of Biosciences and Bioengineering, Indian Institute of Technology, Bombay, Powai, Mumbai-400 076, India | Department of Chemical Engineering, Indian Institute of Technology, Bombay, Powai, Mumbai-400 076, India

Note: [] Corresponding author. Tel.: +91 22 25767223; Fax: +91 22 25723480; E-mail: venks@che.iitb.ac.in

Abstract: Occurrence of multiple upstream activation sites (UASs) is a structural motif that is observed within the promoter of eukaryotic genes for coordinating gene expression. Transcriptional activation depends on the ability of transcriptional activators to bind to its specific UASs, which are kept inaccessible due to the nucleosomal organization of the chromatin. Targeting of chromatin remodeling complexes by a sequence specific transcriptional activator is shown to be detrimental for transcriptional initiation. Here, we analyze such a regulatory structure involving ordered recruitment of transcriptional activators and chromatin remodeling complexes with respect to activation of a flocculin gene, FLO11 involved in the filamentous growth to gain insights into its regulation. We develop a steady state model for the transcriptional regulation of FLO11 by primary transcriptional activators Flo8p, Ste12p, Tec1p and Mss11p, which are under a complex network comprising of cAMP and MAPK pathways. Our analysis predicts that the FLO11 promoter should undergo varying chromatin remodeling activity from partial to complete disassembly depending upon the concentration of Ste12p. This variation should be sensitive and sharply shift to saturate with Ste12p concentration. Overexpression of Ste12p can increase the overall chromatin remodeling activity by increasing the local concentration of remodeling complex through active recruitment. Further, we demonstrate that the chromatin remodeling activity brings about amplification of cAMP and MAPK signal and in absence of either of the signals, the input signal required for the other increases. We also discuss the results obtained from our steady state analysis in respect to other eukaryotic genes.

Keywords: Multiple transcriptional activators, FLO11, STA1, chromatin remodeling, signal integration

Journal: In Silico Biology, vol. 8, no. 3-4, pp. 207-222, 2008