title: Noise minimisation in gene expression switches.
abstract: Gene expression is subject to stochastic variation which leads to fluctuations in the rate of protein production. Recently, a study in yeast at a genomic scale showed that, in some cases, gene expression variability alters phenotypes while, in other cases, these remain unchanged despite fluctuations in the expression of other genes. These studies suggested that noise in gene expression is a physiologically relevant trait and, to prevent harmful stochastic variation in the expression levels of some genes, it can be subject to minimisation. However, the mechanisms for noise minimisation are still unclear. In the present work, we analysed how noise expression depends on the architecture of the cis-regulatory system, in particular on the number of regulatory binding sites. Using analytical calculations and stochastic simulations, we found that the fluctuation level in noise expression decreased with the number of regulatory sites when regulatory transcription factors interacted with only one other bound transcription factor. In contrast, we observed that there was an optimal number of binding sites when transcription factors interacted with many bound transcription factors. This finding suggested a new mechanism for preventing large fluctuations in the expression of genes which are sensitive to the concentration of regulators.
authors.affiliation: Instituto de Física, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Diana
authors.initials: D
authors.lastname: Monteoliva
authors.affiliation: Laboratorio de Metagenómica de Microorganismos, Centro Regional de Estudios Genómicos, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Florencio Varela, Argentina ; Departamento de Informática y Tecnología, Universidad Nacional del Noroeste de la Provincia de Buenos Aires, Pergamino, Buenos Aires, Argentina.
authors.forename: Christina B
authors.initials: CB
authors.lastname: McCarthy
authors.affiliation: Laboratorio de Biología de Sistemas, Centro Regional de Estudios Genómicos, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Luis
authors.initials: L
authors.lastname: Diambra
mesh_terms: D001665:Binding Sites; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D008957:Models, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013269:Stochastic Processes; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors