Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USA.
High-Throughput Sequencing Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USA.
Mol Cell. 2018 Jul 5;71(1):129-141.e8. doi: 10.1016/j.molcel.2018.06.008.
The enhancer regions of the myogenic master regulator MyoD give rise to at least two enhancer RNAs. Core enhancer eRNA (eRNA) regulates transcription of the adjacent MyoD gene, whereas eRNA affects expression of Myogenin in trans. We found that eRNA is recruited at the Myogenin locus, where it colocalizes with Myogenin nascent transcripts. eRNA associates with the cohesin complex, and this association correlates with its transactivating properties. Despite being expressed in undifferentiated cells, cohesin is not loaded on Myogenin until the cells start expressing eRNA, which is then required for cohesin chromatin recruitment and maintenance. Functionally, depletion of either cohesin or eRNA reduces chromatin accessibility, prevents Myogenin activation, and hinders muscle cell differentiation. Thus, eRNA ensures spatially appropriate cohesin loading in trans to regulate gene expression.
肌生成主调控因子 MyoD 的增强子区域至少产生两种增强子 RNA。核心增强子 eRNA（eRNA）调节邻近 MyoD 基因的转录，而 eRNA 则在反式中影响 Myogenin 的表达。我们发现 eRNA 被募集到 Myogenin 基因座，在那里它与 Myogenin 新生转录本共定位。eRNA 与黏合蛋白复合物结合，这种结合与其反式激活特性相关。尽管在未分化细胞中表达，但黏合蛋白复合物直到细胞开始表达 eRNA 才被加载到 Myogenin 上，然后 eRNA 对于黏合蛋白染色质募集和维持是必需的。功能上，耗尽黏合蛋白或 eRNA 都会降低染色质可及性，阻止 Myogenin 激活，并阻碍肌肉细胞分化。因此，eRNA 确保在反式中空间上合适的黏合蛋白加载以调节基因表达。
