Coordinate control of gene expression noise and interchromosomal interactions in a MAP kinase pathway.
In the Saccharomyces cerevisiae pheromone-response pathway, the transcription factor Ste12 is inhibited by two mitogen-activated protein (MAP)-kinase-responsive regulators, Dig1 and Dig2. These two related proteins bind to distinct regions of Ste12 but are redundant in their inhibition of Ste12-dependent gene expression. Here we describe three functions for Dig1 that are non-redundant with those of Dig2. First, the removal of Dig1 results in a specific increase in intrinsic and extrinsic noise in the transcriptional outputs of the mating pathway. Second, in dig1Δ cells, Ste12 relocalizes from the nucleoplasmic distribution seen in wild-type cells into discrete subnuclear foci. Third, genome-wide insertional chromatin immunoprecipitation studies revealed that Ste12-dependent genes have increased interchromosomal interactions in dig1Δ cells. These findings suggest that the regulation of gene expression through long-range gene interactions, a widely observed phenomenon, comes at the cost of increased noise. Consequently, cells may have evolved mechanisms to suppress noise by controlling these interactions.
McCullagh
Emma
E
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, California 94158, USA.
Seshan
Anupama
A
El-Samad
Hana
H
Madhani
Hiten D
HD
D015825:Chromosomes, Fungal / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
C102297:DIG1 protein, S cerevisiae; C102298:DIG2 protein, S cerevisiae; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases