Exploring tissue-specificity in the regulatory landscape of bovine genome

International audience

English. Transcriptomic (mRNA-, totalRNA- and small-RNA-Seq), ATAC- and ChIP-Seq assays were compiled in a catalog of 129 tissue samples collected from 6 individuals of both sexes, different ages, kept in different environments and from 3 divergent dairy and beef cattle breeds/crosses: Holstein, Kinsella composite and Charolais × Holstein F2 crossbred. From the de novo transcriptome assembly, 43,117 gene models including ≥15k potentially novel transcripts were assembled; BovReg expanded the catalog of bovine non-coding RNAs by including non-polyadenylated transcripts (totalRNA assay). Long-read mRNA sequencing (ONT-Seq) is being performed to support predicted isoforms. A total of 1,265 (638 known and 627 novel) miRNAs were detected and, for ≥90%, potential primary transcripts (pri-miRNA) were identified. Interestingly, ~39.71% of the novel miRNAs overlapped with repeats with a strong enrichment for an ancient DNA transposon (Mariner). On average, 105,245 (ATAC), 28,187 (H3K4me3), 152,646 (H3K4me1), 127,855 (H3K27me3), 77,967 (H3K27ac) and 71,868 (CTCF) peaks (q-value ≥0.05) per sample were annotated. Investigating open chromatin regions in the same tissue across the different ages/environment/breeds, differentially accessible regions were identified. By applying nonnegative matrix factorization on regulatory elements × tissue samples, we detected tissue and/or organ-system (muscle, digestive system, etc.) specific components. Using WGS (>30×) from the 6 individuals, ~8.5k CNV and ~400 polymorphic long-terminal repeat transposons were annotated; we highlighted candidates potentially affecting gene expression based on their co-localization with regulatory elements. Tissue-specific unannotated genes, miRNAs/pri-miRNA and regulatory elements were detected contributing to the understanding of vital body functions in bovine. The results presented herein represent a substantial improvement on the regulatory landscape annotation in bovine. The BovReg project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 815668.