Reference: Apostu R and Mackey MC (2012) Mathematical model of GAL regulon dynamics in Saccharomyces cerevisiae. J Theor Biol 293:219-35

Reference Help

Abstract


Genetic switches are prevalent in nature and provide cells with a strategy to adapt to changing environments. The GAL switch is an intriguing example which is not understood in all detail. The GAL switch allows organisms to metabolize galactose, and controls whether the machinery responsible for the galactose metabolism is turned on or off. Currently, it is not known exactly how the galactose signal is sensed by the transcriptional machinery. Here we utilize quantitative tools to understand the S. cerevisiae cell response to galactose challenge, and to analyze the plausible molecular mechanisms underlying its operation. We work at a population level to develop a dynamic model based on the interplay of the key regulatory proteins Gal4p, Gal80p, and Gal3p. To our knowledge, the model presented here is the first to reproduce qualitatively the bistable network behavior found experimentally. Given the current understanding of the GAL circuit induction (Wightman et al., 2008; Jiang et al., 2009), we propose that the most likely in vivo mechanism leading to the transcriptional activation of the GAL genes is the physical interaction between galactose-activated Gal3p and Gal80p, with the complex Gal3p-Gal80p remaining bound at the GAL promoters. Our mathematical model is in agreement with the flow cytometry profiles of wild type, gal3? and gal80? mutant strains from Acar et al. (2005), and involves a fraction of actively transcribing cells with the same qualitative features as in the data set collected by Acar et al. (2010). Furthermore, the computational modeling provides an explanation for the contradictory results obtained by independent laboratories when tackling experimentally the issue of binary versus graded response to galactose induction.

Reference Type
Journal Article
Authors
Apostu R, Mackey MC
Primary Lit For
Additional Lit For
Review For

Interaction Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference