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.

中文翻译：

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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) 在转录调控中发挥着至关重要的作用。虽然在理解 eRNA 介导的表观遗传调控方面取得了重大进展，但对 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组件的识别仍缺乏研究。在这里，我们以猪为模型，利用 H3K27ac 组蛋白 ChIP-seq 和 RNA-seq 数据进行了全面的研究，构建了两个不同猪品种（即恩施黑猪 (ES) 和杜洛克猪）的多个组织的 eRNA 表达谱。除了揭示组织水平上 eRNA 的调控格局外，我们还通过整合 RNA-seq、ChIP-seq、全基因组关联研究 (GWAS) 信号和单核苷酸的增强子调节效应，开发了一种创新的网络构建和细化方法通过自转录活性调控区测序 (STARR-seq) 实验测量多态性 (SNP)。利用这种方法，我们揭示了 eGRN 显着影响肌肉和脂肪组织的生长和发育，并在细胞系模型中鉴定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，而且还提供了一种通用的方法来阐明不同生物体广泛复杂性状背后的 eRNA 介导的转录调控。