Yang Youbing, Li Xinyue, Meng Zhu, Liu Yongjian, Qian Kaifeng, Chu Mingxing, Pan Zhangyuan
College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.
Key Laboratory of Animal Genetics and Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
Front Vet Sci. 2023 Oct 6;10:1239965. doi: 10.3389/fvets.2023.1239965. eCollection 2023.
Super-enhancers (SEs) are clusters of enhancers that act synergistically to drive the high-level expression of genes involved in cell identity and function. Although SEs have been extensively investigated in humans and mice, they have not been well characterized in pigs.
Here, we identified 42,380 SEs in 14 pig tissues using chromatin immunoprecipitation sequencing, and statistics of its overall situation, studied the composition and characteristics of SE, and explored the influence of SEs characteristics on gene expression.
We observed that approximately 40% of normal enhancers (NEs) form SEs. Compared to NEs, we found that SEs were more likely to be enriched with an activated enhancer and show activated functions. Interestingly, SEs showed X chromosome depletion and short interspersed nuclear element enrichment, implying that SEs play an important role in sex traits and repeat evolution. Additionally, SE-associated genes exhibited higher expression levels and stronger conservation than NE-associated genes. However, genes with the largest SEs had higher expression levels than those with the smallest SEs, indicating that SE size may influence gene expression. Moreover, we observed a negative correlation between SE gene distance and gene expression, indicating that the proximity of SEs can affect gene activity. Gene ontology enrichment and motif analysis revealed that SEs have strong tissue-specific activity. For example, the gene with a brain-specific SE shows strong brain-specific expression, and the phenylalanine hydroxylase gene with liver-specific SEs shows strong liver-specific expression.
In this study, we illustrated a body map of SEs and explored their functions in pigs, providing information on the composition and tissue-specific patterns of SEs. This study can serve as a valuable resource of gene regulatory and comparative analyses to the scientific community and provides a theoretical reference for genetic control mechanisms of important traits in pigs.
超级增强子（SEs）是增强子的簇集，它们协同作用以驱动参与细胞特性和功能的基因的高水平表达。尽管SEs已在人类和小鼠中得到广泛研究，但在猪中尚未得到充分表征。
在这里，我们使用染色质免疫沉淀测序在14种猪组织中鉴定出42,380个SEs，并对其整体情况进行统计，研究了SE的组成和特征，并探讨了SEs特征对基因表达的影响。
我们观察到约40%的正常增强子（NEs）形成了SEs。与NEs相比，我们发现SEs更有可能富集有激活的增强子并表现出激活的功能。有趣的是，SEs表现出X染色体缺失和短散在核元件富集，这意味着SEs在性别特征和重复序列进化中起重要作用。此外，与NE相关的基因相比，SE相关的基因表现出更高的表达水平和更强的保守性。然而，具有最大SEs的基因比具有最小SEs的基因具有更高的表达水平，这表明SE的大小可能影响基因表达。此外，我们观察到SE与基因的距离和基因表达之间存在负相关，这表明SEs的接近程度可以影响基因活性。基因本体富集和基序分析表明，SEs具有很强的组织特异性活性。例如，具有脑特异性SE的基因表现出很强的脑特异性表达，而具有肝脏特异性SEs的苯丙氨酸羟化酶基因表现出很强的肝脏特异性表达。
在本研究中，我们绘制了猪SEs的图谱并探索了它们在猪中的功能，提供了有关SEs的组成和组织特异性模式的信息。这项研究可以作为科学界进行基因调控和比较分析的宝贵资源，并为猪重要性状的遗传控制机制提供理论参考。
