Multi-species annotation of transcriptome and chromatin structure in domesticated animals

Abstract

BackgroundComparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells).ResultsRNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically associating domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species.ConclusionsWe report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.

The Landscape of Chromatin Accessibility in Skeletal Muscle During Embryonic Development in Pigs

“…ACRs have been observed to be enriched in promoter regions in many studies, including ours [21,62]. Consistent with our results, the majority of peaks have been mapped to intergenic regions and introns, followed by promoters and exons in approximately equal proportions, and the distributions of peaks in the genome have been similar among different species despite the different genome sizes and degrees of genome annotation [21,60,62,63].…”

“…Among these methods, ATAC-seq is preferred due to its strong advantages: it requires a small input of cells, has a shorter sample-processing period than the other techniques, and has been applied in a variety of studies [17][18][19]. Although several studies have recently performed ATAC-seq on numerous tissues, such as the liver, frontal cortex, lung and longissimus dorsi muscle, the landscape of chromatin accessibility in skeletal muscle during embryonic stages remains poorly demonstrated [20][21][22].…”

Powerful detection of polygenic selection and evidence of environmental adaptation in US beef cattle

“…This identification of candidate genes ignores the possibility significant variants may be acting in trans to change the expression of adaptive genes. Ongoing work to map functional elements of the bovine genome 52,178,179 coupled with sequence-level imputed genotypes will allow us to more accurately identify the important genes, pathways, and networks that contribute to local adaptation.…”

Global Analysis of Transcription Start Sites in the New Ovine Reference Genome (Oar rambouillet v1.0)

“…We were also only able to generate CAGE libraries from one isolated cell type, alveolar macrophages. As demonstrated by the FANTOM5 (Forrest et al, 2014), ENCODE (Birney et al, 2007) and FragENCODE (Foissac et al, 2019) projects, including a diversity of immune cell types, in both activated and inactivated states, in future work would capture additional transcriptional diversity. New technologies, such as single cell sequencing, will allow annotation of cell-specific expressed and regulatory regions of the genome at unprecedented resolution (Papatheodorou et al, 2019).…”