title: Gene properties and chromatin state influence the accumulation of transposable elements in genes.
abstract: Transposable elements (TEs) are mobile DNA sequences found in the genomes of almost all species. By measuring the normalized coverage of TE sequences within genes, we identified sets of genes with conserved extremes of high/low TE density in the genomes of human, mouse and cow and denoted them as 'shared upper/lower outliers (SUOs/SLOs)'. By comparing these outlier genes to the genomic background, we show that a large proportion of SUOs are involved in metabolic pathways and tend to be mammal-specific, whereas many SLOs are related to developmental processes and have more ancient origins. Furthermore, the proportions of different types of TEs within human and mouse orthologous SUOs showed high similarity, even though most detectable TEs in these two genomes inserted after their divergence. Interestingly, our computational analysis of polymerase-II (Pol-II) occupancy at gene promoters in different mouse tissues showed that 60% of tissue-specific SUOs show strong Pol-II binding only in embryonic stem cells (ESCs), a proportion significantly higher than the genomic background (37%). In addition, our analysis of histone marks such as H3K4me3 and H3K27me3 in mouse ESCs also suggest a strong association between TE-rich genes and open-chromatin at promoters. Finally, two independent whole-transcriptome datasets show a positive association between TE density and gene expression level in ESCs. While this study focuses on genes with extreme TE densities, the above results clearly show that the probability of TE accumulation/fixation in mammalian genes is not random and is likely associated with different factors/gene properties and, most importantly, an association between the TE insertion/fixation rate and gene activity status in ES cells.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dixie L
authors.initials: DL
authors.lastname: Mager
mesh_terms: D000818:Animals; D001482:Base Composition; D002417:Cattle; D002843:Chromatin / Q000235:genetics*; D002874:Chromosome Mapping; D004257:DNA Polymerase II / Q000378:metabolism; D004251:DNA Transposable Elements / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism; D015870:Gene Expression; D016678:Genome / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051379:Mice; D016254:Mutagenesis, Insertional; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D013045:Species Specificity; D059467:Transcriptome
chemical_list: D002843:Chromatin; D004251:DNA Transposable Elements; D006657:Histones; D004257:DNA Polymerase II