title: Understanding gene sequence variation in the context of transcription regulation in yeast.
abstract: DNA sequence polymorphism in a regulatory protein can have a widespread transcriptional effect. Here we present a computational approach for analyzing modules of genes with a common regulation that are affected by specific DNA polymorphisms. We identify such regulatory-linkage modules by integrating genotypic and expression data for individuals in a segregating population with complementary expression data of strains mutated in a variety of regulatory proteins. Our procedure searches simultaneously for groups of co-expressed genes, for their common underlying linkage interval, and for their shared regulatory proteins. We applied the method to a cross between laboratory and wild strains of S. cerevisiae, demonstrating its ability to correctly suggest modules and to outperform extant approaches. Our results suggest that middle sporulation genes are under the control of polymorphism in the sporulation-specific tertiary complex Sum1p/Rfm1p/Hst1p. In another example, our analysis reveals novel inter-relations between Swi3 and two mitochondrial inner membrane proteins underlying variation in a module of aerobic cellular respiration genes. Overall, our findings demonstrate that this approach provides a useful framework for the systematic mapping of quantitative trait loci and their role in gene expression variation.
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America. igatviks@broadinstitute.org
authors.forename: Irit
authors.initials: I
authors.lastname: Gat-Viks
authors.forename: Renana
authors.initials: R
authors.lastname: Meller
authors.forename: Martin
authors.initials: M
authors.lastname: Kupiec
authors.forename: Ron
authors.initials: R
authors.lastname: Shamir
mesh_terms: D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D014644:Genetic Variation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029701:Saccharomyces cerevisiae Proteins