Title: | Coordinate control of gene expression noise and interchromosomal interactions in a MAP kinase pathway |
Author(s): | McCullagh E; Seshan A; El-Samad H; Madhani HD; |
Address: | "Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, California 94158, USA" |
ISSN/ISBN: | 1476-4679 (Electronic) 1465-7392 (Print) 1465-7392 (Linking) |
Abstract: | "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 dig1Delta 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 dig1Delta 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" |
Keywords: | "Chromosomes, Fungal/*metabolism *Gene Expression Regulation, Fungal *MAP Kinase Signaling System Mitogen-Activated Protein Kinases/*metabolism Saccharomyces cerevisiae/enzymology/*genetics/growth & development/metabolism Saccharomyces cerevisiae Proteins/;" |
Notes: | "MedlineMcCullagh, Emma Seshan, Anupama El-Samad, Hana Madhani, Hiten D eng R01 GM086379/GM/NIGMS NIH HHS/ R01 GM086379-01/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2010/09/21 Nat Cell Biol. 2010 Oct; 12(10):954-62. doi: 10.1038/ncb2097. Epub 2010 Sep 19" |