Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
Curr Opin Genet Dev. 2013 Oct;23(5):556-61. doi: 10.1016/j.gde.2013.07.002. Epub 2013 Aug 28.
In the last few years, cellular reprogramming has emerged as a means to alter cellular identity and generate diverse cell types for disease modeling, drug testing, and potential therapeutic use. Since each cell type is a result of a specific gene expression profile finely regulated by the activity of a repertoire of transcription factors (TFs), reprogramming approaches have, thus far, been relatively inefficient and based largely on the forced expression of selective cell type-specific TFs. TFs function within the confines of chromatin, and the chromatin states can in turn be modulated by TF activity. Therefore, the knowledge of how chromatin remodeling factors alter chromatin structure, control TF activity and gene expression has led to an improved reprogramming efficiency and extended the number of cellular types that can be generated by cellular reprogramming. Here we review recent insights into the role and mechanisms by which chromatin remodeling, histone modifications, and DNA methylation contribute to cellular differentiation and reprogramming.
在过去的几年中,细胞重编程作为一种改变细胞特性的手段出现,可用于疾病建模、药物测试以及潜在的治疗用途的多种细胞类型的生成。由于每种细胞类型都是特定基因表达谱的结果,而该表达谱又受到转录因子 (TF) 活性的精细调控,因此迄今为止,重编程方法相对效率较低,主要基于选择性细胞类型特异性 TF 的强制表达。TF 在内含子的限制范围内发挥作用,而内含子状态又可以通过 TF 活性进行调节。因此,对染色质重塑因子如何改变染色质结构、控制 TF 活性和基因表达的了解,提高了重编程效率,并扩展了可通过细胞重编程生成的细胞类型的数量。在这里,我们回顾了染色质重塑、组蛋白修饰和 DNA 甲基化在细胞分化和重编程中的作用和机制的最新见解。