PSVII-7 - Putative epigenetic regulating fatty acids content in muscle of Nelore cattle

Abstract: Fatty acid (FA) content plays a significant role in the quality and nutritional composition of beef. However, genetic and epigenetic mechanisms governing FA content in beef are not fully understood. Therefore, we identified putative regulatory genes potentially modulating FA content in Nelore cattle muscle that are also being epigenetically repressed. These genes are called discordantly regulated genes (DRGs). We used genome-wide expression data from muscle samples of Nelore steers, which were selected based on contrasting levels of five specific fatty acids. Our study cohort comprised 15 muscle samples per contrasting group, sourced from an experimental breeding herd, born between 2009 and 2011 and assayed on feedlot at the Brazilian Agricultural Research Corporation (EMBRAPA/Brazil). These animals were sired by 34 unrelated bulls representing prominent genealogies prevalent in Brazil during that period. We identified 48 unique DRGs associated with the content of at least one fatty acid. There were 24 DRGs for conjugated linoleic acid (CLA), 32 for oleic acid (OA), 26 for palmitic acid (PA), 22 for eicosapentaenoic acid (EPA) and 22 for docosahexaenoic acid (DHA). These DRGs play crucial roles in developmental and differentiation processes, aligning with expectations for genes under epigenetic regulation. Notably, 10 DRGs were identified as common regulators across all five FAs (COMP, HOXC10, LBX1, PAX7, PITX2, SIM2, SOX17, TBX15, TBX3 and ZIC4); five DRGs were previously published differentially expressed genes for CLA, 25 were annotated as known bovine transcription factors and one as a known bovine transcription cofactor, further supporting their regulatory potential. To investigate genetic variants associated with epigenetically regulated genomic regions linked to FA traits, we conducted association tests with SNPs proximal to the transcription start sites (TSS) of DRGs. For that we considered a window of 10kb for each side, and the previously published genetic estimated breeding value for the fatty acids in the study. We identified a significant SNP, rs110498194, associated with CLA (FDR < 0.05). This SNP is within an intron of the PITX2 gene, located 7,537 bp downstream of its TSS. PITX2 is a DRG for all five fatty acids and is a known bovine transcription factor. To validate the presence of epigenetic elements within the genomic region associated with CLA, we examined two bovine muscle samples from the FAANG project using the UCSC Genome Browser. We identified ATAC-Seq and ChIP-Seq peaks for CTCF, H3K27ac, H3K27me3, H3K4me1 and H3K4me3, indicating active epigenetic regulation in these genomic regions. Despite the limitations in our predictions, stemming from the enrichment of cell differentiation-related processes and reliance on human-based data, our findings highlight candidate genes implicated in the regulation of fatty acid content in bovine muscle, potentially repressed by epigenetic mechanisms and a SNP involved in this regulation for CLA.