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Oxford University Press (OUP), The Journal of Biochemistry, 2(142), p. 135-144

DOI: 10.1093/jb/mvm151

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

Journal article published in 2007 by Hsih-Te Yang, Chao-Ping Hsu ORCID, Ming-Jing Hwang
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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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 (approximately 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.