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.

Acute and long-term effects of Δ9-tetrahydrocannabinol on object recognition and anxiety-like activity are age- and strain-dependent in mice

“…Strategies such as assessing behavior in a panel of recombinant inbred strains, such as the B6 by D2 cross (BXD RI), allow for genetic mapping of quantitative trait loci (QTLs) or chromosomal regions that may contain genes that influence susceptibility or resistance to THC-related behaviors (Plomin et al, 1991; Williams & Williams, 2017). Newer techniques in RNA and chromatin sequencing also make it possible to identify epigenetic alterations following THC treatment (Scott-Boyer & Deschepper, 2013; Goldowitz et al, 2014; Yeo et al, 2016). These preclinical advances are critical in identifying translational biomarkers of risk and consequences of drug use in human populations (Crabbe, 2016).…”

Dual Linkage of a Locus to Left Ventricular Mass and a Cardiac Gene Co-Expression Network Driven by a Chromosome Domain

“…By analyzing gene expression in different tissues from several mouse RIS, we have previously reported on the existence of chromosome domains that contain genes that could all be linked as cis-eQTLs to one same locus within these domains (which we called “cis-eQTL clusters”) ( 18 ). On the basis of data from hearts of AxB/BxA RIS mice, these domains corresponded to regions averaging 221.9 ± 130 kb and contained in average a cluster of 4.23 ± 1.9 highly co-expressed cis-eQTL genes.…”

“…All processed data are available for public access at GeneNetwork (accession number GN421) 1 . Further analyses, involving genotyping of all 24 RIS and mapping of eQTLs, were performed as described previously ( 18 ). All files with genotypes are available at the following Website: .…”

“…For the majority of such modules, the mQTL was on the same chromosome as the one contributing most genes to the module, with genes originating from that chromosome showing higher connectivity than other genes in the module. Along with the fact that corresponding genomic regions contained increased abundance of polymorphic structural variants, these data suggested that such modules were driven by particular chromosome domains ( 17 , 18 ). Beyond individual c3-eQTLs, it is thus possible that such chromosome domain-driven (CDD) mQTLs link to a quantitative phenotype via coordinate changes in the expression of several genes in proximity to the mQTL.…”

Regulatory effects of theUty/Ddx3ylocus on neighboring chromosome Y genes and autosomal mRNA transcripts in adult mouse non-reproductive cells

“…As this occurred not only in mice, but in humans as well, it may constitute an evolutionary conserved characteristic of MSY genes in vertebrates. Of note, such patterns of co-expression between neighboring genes are rarely seen within vertebrate genomes, and do almost never occur at such high levels 28 . Nonetheless, such characteristics may have emerged within the male chrY because evolutionary forces that are different from those exerted on autosomes 29 have resulted in different types of regulatory mechanism.…”