A subset of unfixed bovine endogenous retroviruses perturb gene expression in cis

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Tang, Lijing | Dupont, Sébastien | Coppieters, Wouter | Georges, Michel | Charlier, Carole | Costa Monteiro Moreira, Gabriel

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International audience. We have established a catalogue of polymorphic endogenous retroviruses (pERV) by mining a dataset of >1000 whole genome sequences (WGS) from two cattle breeds. A total of 1742 pERV loci were detected. We showed that pERV are significantly depleted from genic regions (26% genic – 74% intergenic; p<0.01). Moreover, when genic, a significant bias against sense insertion was observed (40% sense – 60% antisense; p<0.01). We used a direct provirus-based capture method to discriminate between non-solo-LTRs and solo-LTRs pERV. We concluded that the vast majority (83%) of pERV loci exist as solo-LTRs. To assess their individual cis-regulatory effect on testicular parenchyma transcriptomes, we collected >100 fresh samples of sexually mature bulls. Stranded mRNA libraries were built and sequenced (TruSeq mRNA, Illumina). After mapping reads to the reference genome (ARS-UCD1.2) and comparing to a panel of somatic tissues, mature testes exhibited 4-fold more genes with elevated expression and most of those were testis-enhanced, with GO terms enriched for spermatogenesis related processes. Genotypes at pERV loci were obtained for all samples using a combination of direct array-genotyping and/or pERV imputation using our reference WGS dataset. At each pERV locus, systematic cis-perturbation analyses were performed, including differential expression resulting in allelic imbalance, alternative promoter usage, alternative splicing with exon-skipping or exon-capture, or creation of new poly-adenylation signal. A comprehensive analysis of the species-specific re-wiring potential of this young ERV family will be presented. Finally, we highlighted a rare antisense non-solo-LTR pERV insertion in the coding exon 6 of the Centrosomal Protein 126 gene (CEP126) leading to its allele specific transcriptional arrest.

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