Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations

Iván M. Lengyel; Daniele Soroldoni; Andrew C. Oates; Luis G. Morelli

doi:10.4279/pip.060012

Authors

Iván M. Lengyel Departamento de Fisica Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires IFIBA / CONICET
Daniele Soroldoni MRC-National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK
Andrew C. Oates MRC-National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK
Luis G. Morelli Departamento de Fisica Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires IFIBA / CONICET

DOI:

https://doi.org/10.4279/pip.060012

Keywords:

genetic oscillations, negative feedback, cooperativity

Abstract

We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses for how the number of bound repressors affects transcription rate. Effective Hill exponents of the resulting regulatory functions reveal an increase in the nonlinearity of the feedback with the number of binding sites. We identify optimal configurations that maximize the nonlinearity of the feedback. We use a generic model of a biochemical oscillator to show that this increased nonlinearity is reflected in enhanced oscillations, with larger amplitudes over wider oscillatory ranges. Although the study is motivated by genetic oscillations in the zebrafish segmentation clock, our findings may reveal a general principle for gene regulation.

Received: 3 August 2013, Accepted: 20 October 2014; Edited by: G. Mindlin; DOI: http://dx.doi.org/10.4279/PIP.060012

Cite as: I M Lengyel, D Soroldoni, A C Oates, L G Morelli, Papers in Physics 6, 060012 (2014)