Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Cancer Sci. 2019 Aug;110(8):2328-2336. doi: 10.1111/cas.14107. Epub 2019 Jul 10.
Changes of nuclear localization of lineage-specific genes from a transcriptionally inert to permissive environment are a crucial step in establishing the identity of a cell. Noncoding RNA transcription-mediated genome folding and activation of target gene expression have been found in a variety of cell types. Noncoding RNA ThymoD (thymocyte differentiation factor) transcription at superenhancers is essential for mouse T-cell lineage commitment. The cessation of ThymoD transcription abolishes transcription-mediated demethylation, recruiting looping factors such as the cohesin complex, CCCTC-binding factor (CTCF), ultimately leading to the phenotype of severe combined immunodeficiency and T-cell leukemia/lymphoma. In this review, we describe the functional role of RNA polymerase II-mediated transcription at enhancers and in genome folding. We also highlight the involvement of faulty activation or suppression of enhancer transcription and enhancer-promoter interaction in cancer development.
从转录沉默到许可的环境中，谱系特异性基因的核定位变化是建立细胞身份的关键步骤。非编码 RNA 转录介导的基因组折叠和靶基因表达的激活已在多种细胞类型中发现。超增强子上的 ThymoD（胸腺细胞分化因子）转录对于小鼠 T 细胞谱系的决定至关重要。ThymoD 转录的停止会消除转录介导的去甲基化，招募环化因子复合物（如黏合蛋白复合物、CCCTC 结合因子（CTCF），最终导致严重联合免疫缺陷和 T 细胞白血病/淋巴瘤的表型。在这篇综述中，我们描述了 RNA 聚合酶 II 介导的增强子和基因组折叠中的转录的功能作用。我们还强调了增强子转录和增强子-启动子相互作用的错误激活或抑制在癌症发展中的作用。
