Pioneer transcription factors in cell reprogramming.
Pioneer transcription factors in cell reprogramming.
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DOI：
10.1101/gad.253443.114
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发表时间：
2014-12-15
影响因子：
10.5
通讯作者：
Zaret KS
中科院分区：
文献类型：
--
作者：
Iwafuchi-Doi M;Zaret KS
生物化学和基因组学研究表明，具有最高重编程活性的转录因子通常具有与核小体DNA上的靶位点结合的特殊能力，因此充当“先锋因子”，在封闭的染色质中启动事件。Iwafuchi-Doi和Zaret综述了细胞编程和重编程中先锋因子的最新研究，先锋因子如何具有特殊的染色质结合特性，以及染色质结合的促进因子和阻碍因子。真核生物转录因子的一个子集具有将一种细胞重编程为另一种细胞的非凡能力。重编程细胞命运的转录因子总是那些在胚胎发育的初始细胞编程中至关重要的转录因子。为了引发细胞编程或重编程，转录因子必须能够参与在原始细胞中发育沉默且不适合表达的基因。发育沉默的基因通常嵌入被核小体覆盖的“封闭”染色质中，对核酸酶探针（如DNA酶i）不敏感。生化和基因组研究表明，具有最高重编程活性的转录因子通常具有与核小体DNA上的靶位点结合的特殊能力，因此充当“先驱因子”，启动封闭染色质中的事件。其他重编程因子似乎依赖于参与核小体和封闭染色质的先驱因子。然而，核小体被高阶染色质结构遮挡的某些基因组结构域，如异染色质，对先驱因子结合具有抗性。了解先锋因子与封闭染色质结合的方式以及异染色质如何阻止这种结合有望提高我们随意重编程细胞命运的能力，这是本综述的主题。
Biochemical and genomic studies have shown that transcription factors with the highest reprogramming activity often have the special ability to engage their target sites on nucleosomal DNA, thus behaving as “pioneer factors” to initiate events in closed chromatin. This review by Iwafuchi-Doi and Zaret focuses on the most recent studies of pioneer factors in cell programming and reprogramming, how pioneer factors have special chromatin-binding properties, and facilitators and impediments to chromatin binding. A subset of eukaryotic transcription factors possesses the remarkable ability to reprogram one type of cell into another. The transcription factors that reprogram cell fate are invariably those that are crucial for the initial cell programming in embryonic development. To elicit cell programming or reprogramming, transcription factors must be able to engage genes that are developmentally silenced and inappropriate for expression in the original cell. Developmentally silenced genes are typically embedded in “closed” chromatin that is covered by nucleosomes and not hypersensitive to nuclease probes such as DNase I. Biochemical and genomic studies have shown that transcription factors with the highest reprogramming activity often have the special ability to engage their target sites on nucleosomal DNA, thus behaving as “pioneer factors” to initiate events in closed chromatin. Other reprogramming factors appear dependent on pioneer factors for engaging nucleosomes and closed chromatin. However, certain genomic domains in which nucleosomes are occluded by higher-order chromatin structures, such as in heterochromatin, are resistant to pioneer factor binding. Understanding the means by which pioneer factors can engage closed chromatin and how heterochromatin can prevent such binding promises to advance our ability to reprogram cell fates at will and is the topic of this review.
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