Combinatorial control of diverse metabolic and physiological functions by transcriptional regulators of the yeast sulfur assimilation pathway

Allegra A. Petti, R. Scott McIsaac, Olivia Ho-Shing, Harmen J. Bussemaker, David Botstein

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Methionine abundance affects diverse cellular functions, including cell division, redox homeostasis, survival under starvation, and oxidative stress response. Regulation of the methionine biosynthetic pathway involves three DNA-binding proteins-Met31p, Met32p, and Cbf1p. We hypothesized that there exists a "division of labor" among these proteins that facilitates coordination of methionine biosynthesis with diverse biological processes. To explore combinatorial control in this regulatory circuit, we deleted CBF1, MET31, and MET32 individually and in combination in a strain lacking methionine synthase. We followed genome-wide gene expression as these strains were starved for methionine. Using a combination of bioinformatic methods, we found that these regulators control genes in volved in biological processes downstream of sulfur assimilation; many of these processes had not previously been documented as methionine dependent. We also found that the different factors have overlapping but distinct functions. In particular, Met31p and Met32p are important in regulating methionine metabolism, whereas p functions as a "generalist" transcription factor that is not specific to methionine metabolism. In addition, Met31p and Met32p appear to regulate iron-sulfur cluster biogenesis through direct and indirect mechanisms and have distinguishable target specificities. Finally, CBF1 deletion sometimes has the opposite effect on gene expression from MET31 and MET32 deletion.

Original languageEnglish
Pages (from-to)3008-3024
Number of pages17
JournalMolecular biology of the cell
Volume23
Issue number15
DOIs
StatePublished - Aug 1 2012

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