Genome wide analysis of bovine enhancers and promoters across developmental stages in liver

Gene transcription is controlled by functional interactions between promoters and enhancers. Cap analysis of gene expression (CAGE) sequencing has allowed for the accurate annotation of most gene promoters (transcription start sites, TSS) and active enhancers. To date, TSSs and enhancer regions in the bovine genome are poorly characterised. To explore bovine developmental-specific patterns of enhancer-TSS usage and model TSS-enhancer interaction, CAGE-seq was applied to 6 bovine liver samples comprised of two different developmental stages (foetal and adult) obtained from 3 cows and their 3 foetuses. We identified approximately 30k and 20k TSSs and enhancer candidates, respectively, across the liver samples. About 231 significant TSS-enhancer interaction candidates were found by looking for closely spaced TSSs and enhancers that have highly correlated expression levels (r > 0.75; P-value < 0.05). Differential expression between development stages of TSS and enhancer candidates was performed using the Bioconductor package DESeq2 and identified 2050 (6) TSS (enhancer) candidates significantly differentially expressed across developmental stages (P-value < 0.05). The resulting catalogue of TSSs and active enhancers enables classification of developmental-specific TSSs-enhancers and modelling their interaction and provides major target regions for investigation of DNA methylation changes with aging. The information will also be useful in refining regions likely to contain causative mutations for complex traits associated with liver gene expression, such as feed efficiency.