title: Genome-Wide Detection of Gene Coexpression Domains Showing Linkage to Regions Enriched with Polymorphic Retrotransposons in Recombinant Inbred Mouse Strains.
abstract: Although gene coexpression domains have been reported in most eukaryotic organisms, data available to date suggest that coexpression rarely concerns more than doublets or triplets of adjacent genes in mammals. Using expression data from hearts of mice from the panel of AxB/BxA recombinant inbred mice, we detected (according to window sizes) 42-53 loci linked to the expression levels of clusters of three or more neighboring genes. These loci thus formed "cis-expression quantitative trait loci (eQTL) clusters" because their position matched that of the genes whose expression was linked to the loci. Compared with matching control regions, genes contained within cis-eQTL clusters showed much greater levels of coexpression. Corresponding regions showed: (1) a greater abundance of polymorphic elements (mostly short interspersed element retrotransposons), and (2) significant enrichment for the motifs of binding sites for various transcription factors, with binding sites for the chromatin-organizing CCCTC-binding factor showing the greatest levels of enrichment in polymorphic short interspersed elements. Similar cis-eQTL clusters also were detected when we used data obtained with several tissues from BxD recombinant inbred mice. In addition to strengthening the evidence for gene expression domains in mammalian genomes, our data suggest a possible mechanism whereby noncoding polymorphisms could affect the coordinate expression of several neighboring genes.
authors.affiliation: Cardiovascular Biology Research Unit, Institut de recherches cliniques de Montréal (IRCM) and Université de Montréal, Montréal, Québec, H2W 1R7, Canada.
authors.forename: Marie-Pier
authors.initials: MP
authors.lastname: Scott-Boyer
authors.affiliation: Cardiovascular Biology Research Unit, Institut de recherches cliniques de Montréal (IRCM) and Université de Montréal, Montréal, Québec, H2W 1R7, Canada deschec@ircm.qc.ca.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Deschepper
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D004251:DNA Transposable Elements; D015870:Gene Expression; D016678:Genome; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012097:Repressor Proteins; D018626:Retroelements
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D004251:DNA Transposable Elements; D012097:Repressor Proteins; D018626:Retroelements
keywords: clustering of coexpressed genes; genetics of gene expression; quantitative trait loci; structural variants; transposable elements
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