Chao Wang, Choulin Chen, Bowen Lei, Shenghua Qin, Yuanyuan Zhang, Kui Li, Song Zhang, Yuwen Liu
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Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs
Enhancer RNAs (eRNAs) play a crucial role in transcriptional regulation. While significant progress has been made in understanding epigenetic regulation mediated by eRNAs, research on the construction of eRNA-mediated gene regulatory networks (eGRN) and the identification of critical network components that influence complex traits is lacking. Here, employing the pig as a model, we conducted a comprehensive study using H3K27ac histone ChIP-seq and RNA-seq data to construct eRNA expression profiles from multiple tissues of two distinct pig breeds, namely Enshi Black (ES) and Duroc. In addition to revealing the regulatory landscape of eRNAs at the tissue level, we developed an innovative network construction and refinement method by integrating RNA-seq, ChIP-seq, genome-wide association study (GWAS) signals and enhancer-modulating effects of single nucleotide polymorphisms (SNPs) measured by self-transcribing active regulatory region sequencing (STARR-seq) experiments. Using this approach, we unraveled eGRN that significantly influence the growth and development of muscle and fat tissues, and identified several novel genes that affect adipocyte differentiation in a cell line model. Our work not only provides novel insights into the genetic basis of economic pig traits, but also offers a generalizable approach to elucidate the eRNA-mediated transcriptional regulation underlying a wide spectrum of complex traits for diverse organisms.
期刊介绍:
Genetics Selection Evolution invites basic, applied and methodological content that will aid the current understanding and the utilization of genetic variability in domestic animal species. Although the focus is on domestic animal species, research on other species is invited if it contributes to the understanding of the use of genetic variability in domestic animals. Genetics Selection Evolution publishes results from all levels of study, from the gene to the quantitative trait, from the individual to the population, the breed or the species. Contributions concerning both the biological approach, from molecular genetics to quantitative genetics, as well as the mathematical approach, from population genetics to statistics, are welcome. Specific areas of interest include but are not limited to: gene and QTL identification, mapping and characterization, analysis of new phenotypes, high-throughput SNP data analysis, functional genomics, cytogenetics, genetic diversity of populations and breeds, genetic evaluation, applied and experimental selection, genomic selection, selection efficiency, and statistical methodology for the genetic analysis of phenotypes with quantitative and mixed inheritance.