Fus3-triggered Tec1 degradation modulates mating transcriptional output during the pheromone response.
The yeast transcription factor Ste12 controls both mating and filamentation pathways. Upon pheromone induction, the mitogen-activated protein kinases, Fus3 and Kss1, activate Ste12 by relieving the repression of two functionally redundant Ste12 inhibitors, Dig1 and Dig2. Mating genes are controlled by the Ste12/Dig1/Dig2 complex through Ste12-binding sites, whereas filamentation genes are regulated by the Tec1/Ste12/Dig1 complex through Tec1-binding sites. The two Ste12 complexes are mutually exclusive. During pheromone response, Tec1 is degraded upon phosphorylation by Fus3, preventing cross-activation of the filamentation pathway. Here, we show that a stable Tec1 also impairs the induction of mating genes. A mathematical model is developed to capture the dynamic formation of the two Ste12 complexes and their interactions with pathway-specific promoters. By model simulations and experimentation, we show that excess Tec1 can impair the mating transcriptional output because of its ability to sequester Ste12, and because of a novel function of Dig2 for the transcription of mating genes. We suggest that Fus3-triggered Tec1 degradation is an important part of the transcriptional induction of mating genes during the pheromone response.
Chou
Song
S
Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.
Zhao
Su
S
Song
You
Y
Liu
Haoping
H
Nie
Qing
Q
D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D009154:Mutation; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012098:Reproduction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012724:Sex Attractants / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C102297:DIG1 protein, S cerevisiae; C102298:DIG2 protein, S cerevisiae; D004268:DNA-Binding Proteins; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012724:Sex Attractants; C069926:TEC1 protein, S cerevisiae; D014157:Transcription Factors; C075580:FUS3 protein, S cerevisiae; C541984:KSS1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases