Recently, Professor Zhao Shuhong, along with Professor Li Xinyun and his team, has created an extensive genomic map with information on pig genomic promoters, enhancers, open chromatin regions, and 3D genomes covering the widest range of species information and tissue types, identified a large number of cis-regulatory elements and regulatory region mutation loci, and revealed potential regulatory mechanisms that influence pig phenotypic variations. This work lays the foundation on enhancing the efficiency of pig genomic breeding through the application of functional SNP loci.

The Encyclopedia of DNA Elements (ENCODE) Project aims to comprehensively annotate functional elements in the genome, while the functional annotation of regulatory elements serves as a crucial foundation for resolving phenotypic variations and gene regulatory mechanisms. Despite the completion of the domestic pig genome sequencing project, which marked the new era in pig genetic breeding research, study on the functional aspects of the non-coding regions, constituting 98% of the genome, has been still limited. Additionally, the annotation of regulatory elements remains unclear, which severely hampers the molecular mechanism analysis of economic traits in pigs and the innovation of genomic breeding technologies.

To overcome this bottleneck, Associate Researcher Zhao Yunxia, Dr. Hou Ye, and Ph.D. student Xu Yueyuan, together with their team, have independently established a comprehensive research technology system for studying epigenetic regulation in pig tissues by using several omics technologies such as ChIP-seq, ATAC-seq, RNA-seq, and Hi-C, and obtained 199 sets of epigenetic regulatory data from 12 different types of tissues by taking big lean white pigs, Duroc pigs, fatty Enshi black pigs and Meishan pigs as the research objects. This research has identified over 220,000 regulatory elements and 3,316 novel transcripts in the pig genome, further elucidated the characteristics of super-enhancers and active promoters in the pig genome, and elaborated the tissue specificity of the pig genomic regulatory elements and the impact of their 3D spatial structure on gene expression regulation, which has provided new insights into the functional genomics and trait regulation mechanisms in pigs.

Genomic Cis-Regulatory Elements and 3D Chromatin Structures in Different Pig Breeds

Due to the lag in the exploration of regulatory elements and functional region mutations in the pig genome, the functional loci cannot be adequately distinguished from molecular markers. Consequently, when designing genomic breeding chips, the information related to functional regions and loci cannot be fully utilized, thereby influencing the improvement of the genomic breeding efficiency. This study has integrated regulatory elements, 3D genome, and genome-wide association analysis (GWAS) information to elucidate the distribution characteristics of GWAS loci for important pig traits around regulatory elements, identified candidate causal mutations for some important traits, and also identified a batch of potentially functional SNPs by integrating genomic mutations, epigenetic modifications, 3D genomes and gene expression variations among different breeds. The aforementioned achievements have provided a wealth of data and information for the innovation and improvement of genomic breeding technologies, and opened up new avenues to accelerate genetic enhancements of economic traits in pigs.

The Distribution of GWAS Loci Near Enhancers in the Pig Genome

[Abstract]

Although major advances in genomics have initiated an exciting new era of research, a lack of information regarding cis-regulatory elements has limited the genetic improvement or manipulation of pigs as a meat source and biomedical model. Here, we systematically characterize cis-regulatory elements and their functions in 12 diverse tissues from four pig breeds by adopting similar strategies as the ENCODE and Roadmap Epigenomics projects, which include RNA-seq, ATAC-seq, and ChIP-seq. In total, we generate 199 datasets and identify more than 220,000 cis-regulatory elements in the pig genome. Surprisingly, we find higher conservation of cis-regulatory elements between human and pig genomes than those between human and mouse genomes. Furthermore, the differences of topologically associating domains between the pig and human genomes are associated with morphological evolution of the head and face. Beyond generating a major new benchmark resource for pig epigenetics, our study provides basic comparative epigenetic data relevant to using pigs as models in human biomedical research.

Paper Link:https://www.nature.com/articles/s41467-021-22448-x