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Journal of Biochemistry Advance Access originally published online on July 25, 2007
Journal of Biochemistry 2007 142(2):135-144; doi:10.1093/jb/mvm151
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© 2007 The Japanese Biochemical Society.

An Analytical Rate Expression for the Kinetics of Gene Transcription Mediated by Dimeric Transcription Factors

Hsih-Te Yang1,3, Chao-Ping Hsu2 and Ming-Jing Hwang3,*

1Institute of Biochemistry and Molecular Biology, National Yang-Ming University; 2Institute of Chemistry and 3Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

*To whom correspondence should be addressed. Tel: +886-2-2789-9033, Fax: +886-2-2788-7641, E-mail: mjhwang{at}ibms.sinica.edu.tw

Received April 17, 2007; Accepted June 1, 2007


  Abstract

To model gene transcription kinetics, empirical fitting with the Hill function or S-system is often used. In this study, we derived an analytical expression for gene transcription rates in a manner similar to that developed for enzyme kinetics to describe the kinetics of gene transcription mediated by dimeric transcription factors (TFs) such as Gcn4p, a Saccharomyces cerevisiae master gene regulator. We showed that the analytical rate expression and its parameters estimated from several sets of experimental data could accurately reproduce the experimentally measured promoter-binding activity of Gcn4p. Furthermore, the analytical rate expression allowed us to derive analytically, rather than fit empirically, the parameters of the Hill function and S-system for use in modelling transcription kinetics. We found that a plot of gene transcription rate against Gcn4p concentration gave a sigmoidal dose-response curve with a positive co-operativity Hill coefficient (~1.25), in accordance with previous experimental findings on the promoter binding of dimeric TFs. The characteristics of the dose-response curve around the estimated cellular Gcn4p concentration suggest that transcription regulation is efficiently controlled under physiological conditions. This work is a useful initial step towards analytically modelling and simulating complicated gene transcription networks.

Key Words: enzyme kinetics, gene transcription modelling, Hill function, S-system, transcription kinetics

Abbreviations: MM, Michaelis–Menten; PIC, pre-initiation complex; TF, transcription factor


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