Cell Biology

Turn Down the Noise

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Science  29 Oct 2010:
Vol. 330, Issue 6004, pp. 561
DOI: 10.1126/science.330.6004.561-b

Many cellular signaling pathways are now sufficiently well mapped to allow more sophisticated investigation of their regulation and of how the range of physiological states that a cell can achieve is determined by the regulatory network structure. One well-studied pathway is that initiated by mating pheromone in yeast. The binding of pheromone to its receptor initiates a signaling pathway that ultimately causes changes in the transcription of genes required to reorganize the cell for mating. McCullagh et al. explored why this pathway contains two redundant components, Dig1 and Dig2, both proteins that bind to and inhibit the transcription factor Ste12 in cells that have been exposed to mating pheromone. Although either protein alone is sufficient to inhibit Ste12-mediated transcription, deletion of the gene that encodes Dig1 revealed several distinct functions. Dig1-deficient cells had increased the variation or “noise” in the amount of transcription of a target gene regulated by Ste12. These cells also exhibited disrupted intranuclear localization of Ste12 and increased interchromosomal interactions of Ste12-regulated genes. These changes may be because the region of Ste12 that interacts with Dig1 is also able to interact with other proteins. Thus, in the absence of Dig1, the interactions between Ste12 and its target genes are not as well coordinated, which results in an increase in noise in the system. Such long-range interactions between genes could be important for coordinating gene expression, but these analyses indicate that such regulation comes at the cost of increased variability in signal output.

Nat. Cell. Biol. 12, 954 (2010).

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