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  3. Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs

Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs

  • Genet Sel Evol. 2024 Apr 9;56(1):28. doi: 10.1186/s12711-024-00897-4.
Chao Wang # 1 2 3,  Choulin Chen # 1 2 3,  Bowen Lei 1 2 3,  Shenghua Qin 1 2,  Yuanyuan Zhang 1 2 4 5,  Kui Li 1 2,  Song Zhang 6 7,  Yuwen Liu 8 9 10 11
Affiliations

Affiliations

  • 1 Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, People's Republic of China.
  • 2 Innovation Group of Pig Genome Design and Breeding, Research Centre for Animal Genome, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, People's Republic of China.
  • 3 Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
  • 4 School of Life Sciences, Henan University, Kaifeng, 475004, People's Republic of China.
  • 5 Shenzhen Research Institute of Henan University, Shenzhen, 518000, People's Republic of China.
  • 6 Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, People's Republic of China. zhangsong0001@163.com.
  • 7 Innovation Group of Pig Genome Design and Breeding, Research Centre for Animal Genome, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, People's Republic of China. zhangsong0001@163.com.
  • 8 Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, People's Republic of China. liuyuwen@caas.cn.
  • 9 Innovation Group of Pig Genome Design and Breeding, Research Centre for Animal Genome, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, People's Republic of China. liuyuwen@caas.cn.
  • 10 Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China. liuyuwen@caas.cn.
  • 11 Kunpeng Institute of Modern Agriculture at Foshan, Chinese Academy of Agricultural Sciences, Foshan, 528226, People's Republic of China. liuyuwen@caas.cn.
  • # Contributed equally.
PMID: 38594607 DOI: 10.1186/s12711-024-00897-4
Abstract

Background: 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.

Results: 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.

Conclusions: 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.

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