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

IF 3.6 1区农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Genetics Selection Evolution Pub Date : 2024-04-09 DOI:10.1186/s12711-024-00897-4

Chao Wang, Choulin Chen, Bowen Lei, Shenghua Qin, Yuanyuan Zhang, Kui Li, Song Zhang, Yuwen Liu

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引用次数: 0

Abstract

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.

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构建 eRNA 介导的基因调控网络，探索猪肌肉和脂肪相关性状的遗传基础

增强子 RNA（eRNA）在转录调控中起着至关重要的作用。虽然在了解 eRNA 介导的表观遗传调控方面已经取得了重大进展，但有关 eRNA 介导的基因调控网络（eGRN）的构建以及影响复杂性状的关键网络成分的鉴定研究仍然缺乏。在这里，我们以猪为模型，利用 H3K27ac 组蛋白 ChIP-seq 和 RNA-seq 数据进行了一项综合研究，构建了恩施黑猪（ES）和杜洛克猪（Duroc）这两个不同猪种多个组织的 eRNA 表达谱。除了揭示组织水平的 eRNA 调控图谱外，我们还开发了一种创新的网络构建和完善方法，将 RNA-seq、ChIP-seq、全基因组关联研究（GWAS）信号和自转录活性调控区测序（STAR-seq）实验测得的单核苷酸多态性（SNPs）的增强子调控效应整合在一起。利用这种方法，我们揭示了对肌肉和脂肪组织的生长发育有显著影响的 eGRN，并在细胞系模型中发现了几个影响脂肪细胞分化的新基因。我们的工作不仅为经济猪性状的遗传基础提供了新的见解，还提供了一种可推广的方法来阐明 eRNA 介导的转录调控对各种生物的复杂性状的影响。

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来源期刊

Genetics Selection Evolution 生物-奶制品与动物科学

CiteScore

6.50

自引率

9.80%

发文量

审稿时长

1 months

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.