1. Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
- Author
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Andrew C. Oates, Daniele Soroldoni, Iván M. Lengyel, and Luis G. Morelli
- Subjects
Materials Science (miscellaneous) ,Molecular Networks (q-bio.MN) ,cooperativity ,Ciencias Físicas ,General Physics and Astronomy ,Repressor ,FOS: Physical sciences ,Cooperativity ,Otras Ciencias Físicas ,Article ,genetic oscillations ,purl.org/becyt/ford/1 [https] ,Quantitative Biology::Subcellular Processes ,03 medical and health sciences ,0302 clinical medicine ,Negative feedback ,Quantitative Biology - Molecular Networks ,Statistical physics ,Physics - Biological Physics ,Physical and Theoretical Chemistry ,Binding site ,lcsh:Science ,NEGATIVE FEEDBACK ,Transcription factor ,030304 developmental biology ,Physics ,Regulation of gene expression ,0303 health sciences ,Quantitative Biology::Molecular Networks ,NONLINEAR DYNAMICS ,Cooperative binding ,Function (mathematics) ,negative feedback ,purl.org/becyt/ford/1.3 [https] ,GENETIC OSCILLATIONS ,Quantitative Biology::Genomics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,lcsh:QC1-999 ,Biological Physics (physics.bio-ph) ,FOS: Biological sciences ,lcsh:Q ,Adaptation and Self-Organizing Systems (nlin.AO) ,030217 neurology & neurosurgery ,lcsh:Physics ,CIENCIAS NATURALES Y EXACTAS - 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., 11 pages, 8 figures
- Published
- 2021