Yu Lin1,9, Jing Li1,9, Yiren Gu2,3,9, Long Jin1,9, Jingyi Bai1, Jiaman Zhang1, Yujie Wang1, Pengliang Liu1, Keren Long1, Mengnan He1, Diyan Li4, Can Liu1, Ziyin Han1, Yu Zhang1, Xiaokai Li1, Bo Zeng1, Lu Lu1, Fanli Kong1, Ying Sun1,5, Yongliang Fan1, Xun Wang1, Tao Wang4, An'an Jiang1, Jideng Ma1, Linyuan Shen1, Li Zhu1, Yanzhi Jiang1, Guoqing Tang1, Xiaolan Fan1, Qingyou Liu6, Hua Li6, Jinyong Wang7,8, Li Chen7,8, Liangpeng Ge7,8, Xuewei Li1, Qianzi Tang1 and Mingzhou Li1 1State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; 2College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu 610041, China; 3Animal Breeding and Genetics Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Chengdu 610066, China; 4School of Pharmacy, Chengdu University, Chengdu 610106, China; 5Institute of Geriatric Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China; 6Animal Molecular Design and Precise Breeding Key Laboratory of Guangdong Province, School of Life Science and Engineering, Foshan University, Foshan 528225, China; 7Pig Industry Sciences Key Laboratory of Ministry of Agriculture and Rural Affairs, Chongqing Academy of Animal Sciences, Chongqing 402460, China; 8National Center of Technology Innovation for Pigs, Chongqing 402460, China

↵9 These authors contributed equally to this work.

Corresponding authors: lijing_2020sicau.edu.cn, tangqianzisicau.edu.cn, mingzhou.lisicau.edu.cn Abstract

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic differences of long-range promoter–enhancer contacts, which likely contribute to the phenotypic differences between the parental pig breeds. We also observe the fine structure of somatically paired homologous chromosomes in the pig genome, which has a functional implication genome-wide. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, as well as the possible consequential phenotypic changes in mammals.

Footnotes

[Supplemental material is available for this article.]

Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.278101.123.

Freely available online through the Genome Research Open Access option.

Received May 16, 2023. Accepted February 15, 2024.