Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
Mol Cell. 2013 Sep 12;51(5):606-17. doi: 10.1016/j.molcel.2013.07.022. Epub 2013 Aug 29.
Transcription factors and DNA regulatory binding motifs are fundamental components of the gene regulatory network. Here, by using genome-wide binding profiling, we show extensive occupancy of transcription factors of myogenesis (MyoD and Myogenin) at extragenic enhancer regions coinciding with RNA synthesis (i.e., eRNA). In particular, multiple regions were transcribed to eRNA within the regulatory region of MYOD1, including previously characterized distal regulatory regions (DRR) and core enhancer (CE). While (CE)RNA enhanced RNA polymerase II (Pol II) occupancy and transcription at MYOD1, (DRR)RNA acted to activate the downstream myogenic genes. The deployment of transcriptional machinery to appropriate loci is contingent on chromatin accessibility, a rate-limiting step preceding Pol II assembly. By nuclease sensitivity assay, we found that eRNAs regulate genomic access of the transcriptional complex to defined regulatory regions. In conclusion, our data suggest that eRNAs contribute to establishing a cell-type-specific transcriptional circuitry by directing chromatin-remodeling events.
转录因子和 DNA 调控结合基序是基因调控网络的基本组成部分。在这里，我们通过全基因组结合谱分析，发现肌肉发生（MyoD 和 Myogenin）转录因子广泛占据与 RNA 合成（即 eRNA）偶联的基因外增强子区域。特别是，在 MYOD1 的调控区域内，有多个区域转录为 eRNA，包括先前表征的远端调控区域（DRR）和核心增强子（CE）。虽然（CE）RNA 增强了 RNA 聚合酶 II（Pol II）在 MYOD1 上的占据和转录，但（DRR）RNA 则激活下游的肌生成基因。转录机制在适当位置的部署取决于染色质可及性，这是 Pol II 组装之前的限速步骤。通过核酸酶敏感性测定，我们发现 eRNAs 通过调控转录复合物对特定调控区域的基因组访问。总之，我们的数据表明，eRNAs 通过指导染色质重塑事件，有助于建立细胞类型特异性的转录电路。
