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Single-Cell Resolution 3D Genomic Landscape of Hybrid Pigs Resolved

ZhangQingDan,ZhangQingDan Fri, Mar 22 2024 10:55 AM EST

China is the world's largest pork producer, with 727 million pigs slaughtered in 2023, accounting for 54.89% of the global total. Pigs play a crucial role in the national economy, food security, and social stability. Identifying and characterizing key genomic variations that influence important economic traits in pigs, discovering breeding targets, and innovatively applying them in practical breeding can effectively accelerate the development of new, high-quality, and high-yield pig breeds (lines). Therefore, systematically identifying regulatory elements in the pig genome, analyzing their involvement in long-range 3D genomic interactions, and investigating the impact of non-coding sequence variations on gene transcription regulation are of great significance for identifying and clarifying molecular targets with important breeding value.

Existing studies have shown that homologous chromosomes in diploid organisms differ in gene transcription, epigenetic modifications, chromatin accessibility, and chromatin replication timing. However, current 3D genome studies typically analyze the average chromatin spatial conformation features of the diploid genome, lacking an effective way to resolve the structural and regulatory differences between homologous chromosomes.

Recently, the journal Genome Research published a paper titled "Single-Cell Resolution 3D Genomic Landscape of Hybrid Pigs" led by the College of Animal Science and Technology and the National Key Laboratory of Pig and Poultry Breeding, Sichuan Agricultural University.

This study constructed reciprocal F1 populations of Chinese indigenous pig breeds—the Tibetan pig and the European breed—the Berkshire pig. It used the in situ Hi-C technique to reconstruct single-cell-based 3D genome maps of representative tissues from different germ layers, such as skeletal muscle. The study analyzed the differences in chromatin spatial conformation at multiple scales, including compartmentalization, topologically associating domains (TADs), and promoter-enhancer interactions (PEIs), between homologous chromosomes, tissues, reciprocal crosses, and Chinese and European pig breeds. It refined the understanding of the high-order structural features of homologous chromosomes in the pig genome. The study found that the spatial conformation differences between homologous chromosomes are closely related to the phenomenon of genomic imprinting.

Meanwhile, this study quantified the impact of genomic sequence variations and histone modifications (H3K4me3 and H3K27ac) on long-range promoter-enhancer interactions at the single-cell level. It speculates that the interaction changes caused by sequence or epigenetic differences may be important factors leading to the significant differences in skeletal muscle phenotypes between Chinese and European parent pig breeds.

The results of this study provide new insights into the mechanisms of chromatin spatial conformation regulating gene transcription in pigs and provide important basic data and theoretical support for the development of molecular breeding. 65fbe509e4b03b5da6d0b900.jpg

Three-dimensional spatial conformation of homologous chromosomes in hybrid pigs

Provided by Sichuan Agricultural University.

This research was funded by the National Key R&D Program of China titled "Protein Machinery and Regulation of Life Processes" and the Sichuan Province's "14th Five-Year" major scientific and technological project for Sichuan pigs.

Related paper information: http://doi.org/10.1101/gr.278101.123