Author: ["Emma McCullagh","Anupama Seshan","Hana El-Samad","Hiten D. Madhani"]
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Abstract
In yeast, the MAPK-responsive protein Dig1 regulates Ste12 transcription factor activity in response to pheromone. Dig1 is now shown to prevent long-range interchromosomal interactions between Ste12-target genes, dampening transcriptional 'noise'. 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.Cite this article
McCullagh, E., Seshan, A., El-Samad, H. et al. Coordinate control of gene expression noise and interchromosomal interactions in a MAP kinase pathway. Nat Cell Biol 12, 954–962 (2010). https://doi.org/10.1038/ncb2097 