title: Dual feedback loops in the GAL regulon suppress cellular heterogeneity in yeast.
abstract: Transcriptional noise is known to be an important cause of cellular heterogeneity and phenotypic variation. The extent to which molecular interaction networks may have evolved to either filter or exploit transcriptional noise is a much debated question. The yeast genetic network regulating galactose metabolism involves two proteins, Gal3p and Gal80p, that feed back positively and negatively, respectively, on GAL gene expression. Using kinetic modeling and experimental validation, we demonstrate that these feedback interactions together are important for (i) controlling the cell-to-cell variability of GAL gene expression and (ii) ensuring that cells rapidly switch to an induced state for galactose uptake.
authors.affiliation: Institute for Systems Biology, 1441 N 34th Street, Seattle, Washington 98103, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ramsey
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Orrell
authors.forename: Marcello
authors.initials: M
authors.lastname: Marelli
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Petersen
authors.forename: Pedro
authors.initials: P
authors.lastname: de Atauri
authors.forename: Hamid
authors.initials: H
authors.lastname: Bolouri
authors.forename: John D
authors.initials: JD
authors.lastname: Aitchison
mesh_terms: D003198:Computer Simulation; D025461:Feedback, Physiological; D005690:Galactose / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008957:Models, Genetic; D018085:Regulon; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism
chemical_list: D005690:Galactose