Zuloaga Rodrigo, Garrido Camila, Ahumada-Langer Luciano, Galaz José Luis, Ugarte Giorgia Daniela, Molina Alfredo, Valdés Juan Antonio
Programa de Doctorado en Biotecnología, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile.
Laboratorio de Biotecnología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, Chile.
Int J Mol Sci. 2025 Jun 25;26(13):6079. doi: 10.3390/ijms26136079.
Cortisol, the main glucocorticoid in teleost, plays a central role in mediating the physiological response to stress by regulating metabolism, immune function, and growth. While its transcriptional effects are well known, its role in modulating chromatin accessibility in fish skeletal muscle remains poorly understood. In this study, we investigated the epigenomic and transcriptomic changes induced by cortisol in a juvenile rainbow trout's () skeletal muscle using ATAC-seq and RNA-seq. Fish were treated with a single intraperitoneal dose of cortisol (10 mg/kg) or vehicle, and muscle samples were collected 3 h post-treatment. ATAC-seq analysis revealed a total of 163,802 differentially accessible regions (DARs), with an important enrichment of open regions near transcription start sites and promoters. A total of 1612 and 1746 differentially accessible genes (DAGs) were identified in the cortisol and control groups, respectively. Motif enrichment analysis identified 89 transcription factors to be significantly enriched, among which key stress-responsive regulators such as Fos, AP-1, FoxO1/3, Mef2a/b/c, Klf5/10, and ATF4 were prominently represented. RNA-seq analysis identified 4050 differentially expressed genes (DEGs), with 2204 upregulated genes involved in autophagy, mitophagy, and FoxO signaling, while 1864 downregulated genes were enriched in spliceosome and chromatin remodeling pathways. Integrative analysis revealed 174 overlapping genes between ATAC-seq and RNA-seq datasets, highlighting pathways linked to autophagy and ATP-dependent chromatin remodeling. Four selected DEGs (, , , ) were validated by qPCR, showing high concordance with transcriptomic data. These findings provide new insights into cortisol-mediated regulation of chromatin dynamics and gene expression in teleost skeletal muscle and underscore the importance of epigenetic mechanisms in fish stress responses.
皮质醇是硬骨鱼中的主要糖皮质激素，通过调节代谢、免疫功能和生长，在介导对压力的生理反应中发挥核心作用。虽然其转录作用已广为人知，但其在调节鱼类骨骼肌染色质可及性方面的作用仍知之甚少。在本研究中，我们使用ATAC-seq和RNA-seq研究了皮质醇在幼年虹鳟鱼骨骼肌中诱导的表观基因组和转录组变化。鱼通过腹腔注射单剂量皮质醇（10 mg/kg）或溶剂进行处理，并在处理后3小时收集肌肉样本。ATAC-seq分析共揭示了163,802个差异可及区域（DAR），转录起始位点和启动子附近的开放区域有重要富集。在皮质醇组和对照组中分别鉴定出1612个和1746个差异可及基因（DAG）。基序富集分析确定了89个转录因子显著富集，其中Fos、AP-1、FoxO1/3、Mef2a/b/c、Klf5/10和ATF4等关键应激反应调节因子占显著比例。RNA-seq分析鉴定出4050个差异表达基因（DEG），其中2204个上调基因参与自噬、线粒体自噬和FoxO信号传导，而1864个下调基因富集于剪接体和染色质重塑途径。综合分析揭示了ATAC-seq和RNA-seq数据集之间的174个重叠基因，突出了与自噬和ATP依赖的染色质重塑相关的途径。通过qPCR验证了四个选定的DEG（、、、），与转录组数据显示出高度一致性。这些发现为皮质醇介导的硬骨鱼骨骼肌染色质动态和基因表达调控提供了新见解，并强调了表观遗传机制在鱼类应激反应中的重要性。
