Chromatin modulators as facilitating factors in cellular reprogramming

Chromatin modulators as facilitating factors in cellular reprogramming
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DOI:
10.1016/j.gde.2013.07.002
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发表时间:
2013-10-01
影响因子:
4
通讯作者:
Bruneau, Benoit G.
Bruneau, Benoit G.
中科院分区:
生物学2区
文献类型:
--
作者:
Luna-Zurita, Luis;Bruneau, Benoit G.

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在过去的几年里,细胞重新编程已经成为一种改变细胞身份和产生不同类型细胞的手段,用于疾病建模、药物测试和潜在的治疗用途。由于每种细胞类型都是特定基因表达谱的结果,这些基因表达谱受到转录因子(TF)活性的精细调控,到目前为止,重新编程的方法相对效率较低,主要基于选择性细胞类型特异性转录因子的强制表达。TFS在染色质的范围内发挥作用,而染色质的状态又可以受到TF活性的调节。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已经导致了重新编程效率的提高,并扩大了细胞重新编程可以产生的细胞类型的数量。在这里,我们回顾了对染色质重塑、组蛋白修饰和DNA甲基化促进细胞分化和重新编程的作用和机制的最新见解。
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.