Scientific Publications

Understanding gene sequence variation in the context of transcription regulation in yeast.

Publication TypeJournal Article
AuthorsGat-Viks, I., Meller R., Kupiec M., and Shamir R.
AbstractDNA 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.
Year of Publication2010
JournalPLoS genetics
Volume6
Issue1
Pagese1000800
Date Published (YYYY/MM/DD)2010/01/01
ISSN Number1553-7390
DOI10.1371/journal.pgen.1000800
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/20066030?dopt=Abstract