Nashun Buhe, Hill Peter W S, Hajkova Petra
Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, UK.
Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, UK
EMBO J. 2015 May 12;34(10):1296-308. doi: 10.15252/embj.201490649. Epub 2015 Mar 27.
Cell identity is a reflection of a cell type-specific gene expression profile, and consequently, cell type-specific transcription factor networks are considered to be at the heart of a given cellular phenotype. Although generally stable, cell identity can be reprogrammed in vitro by forced changes to the transcriptional network, the most dramatic example of which was shown by the induction of pluripotency in somatic cells by the ectopic expression of defined transcription factors alone. Although changes to cell fate can be achieved in this way, the efficiency of such conversion remains very low, in large part due to specific chromatin signatures constituting an epigenetic barrier to the transcription factor-mediated reprogramming processes. Here we discuss the two-way relationship between transcription factor binding and chromatin structure during cell fate reprogramming. We additionally explore the potential roles and mechanisms by which histone variants, chromatin remodelling enzymes, and histone and DNA modifications contribute to the stability of cell identity and/or provide a permissive environment for cell fate change during cellular reprogramming.
细胞身份是细胞类型特异性基因表达谱的一种反映，因此，细胞类型特异性转录因子网络被认为是特定细胞表型的核心。尽管细胞身份通常是稳定的，但通过对转录网络进行强制改变，可在体外对其进行重编程，其中最显著的例子是仅通过异位表达特定转录因子就可诱导体细胞产生多能性。尽管通过这种方式可以实现细胞命运的改变，但这种转化的效率仍然非常低，这在很大程度上是由于特定的染色质特征构成了转录因子介导的重编程过程的表观遗传障碍。在这里，我们讨论细胞命运重编程过程中转录因子结合与染色质结构之间的双向关系。我们还探讨了组蛋白变体、染色质重塑酶以及组蛋白和DNA修饰在细胞身份稳定性方面的潜在作用和机制，以及它们在细胞重编程过程中为细胞命运改变提供宽松环境的作用和机制。
