Switching of the core transcription machinery during myogenesis
Switching of the core transcription machinery during myogenesis
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DOI：
10.1101/gad.1583407
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发表时间：
2007-09-01
影响因子：
10.5
通讯作者：
Tjian, Robert
中科院分区：
文献类型：
--
作者：
Deato, Maria Divina E.;Tjian, Robert
控制细胞分化的转录机制通常包括序列特异性 DNA 结合蛋白和染色质修饰活性。这些调节因素被认为对于驱动增殖和终末分化的不同程序是必要且充分的。相比之下，基础转录装置对协调细胞特异性基因表达的潜在贡献却知之甚少。为了探索控制分化的替代机制，我们评估了核心启动子识别复合物 TFIID 在骨骼肌发生过程中的命运。在此，我们报道，成肌细胞向肌管的分化涉及典型的 Holo-TFIID 的破坏并被新型 TRF3/TAF3（TBP 相关因子 3/TATA 结合蛋白相关因子 3）复合物取代。这种核心启动子复合物的转换为生物体提供了一种简单而有效的方法，可以选择性地开启一个转录程序，同时沉默许多其他转录程序。尽管这种剧烈但简约的转录开关之前没有引起我们的注意，但它可能代表了调节细胞类型特异性终末分化的更普遍的机制。
Transcriptional mechanisms that govern cellular differentiation typically include sequence-specific DNA-binding proteins and chromatin-modifying activities. These regulatory factors are assumed necessary and sufficient to drive both divergent programs of proliferation and terminal differentiation. By contrast, potential contributions of the basal transcriptional apparatus to orchestrate cell-specific gene expression have been poorly explored. In order to probe alternative mechanisms that control differentiation, we have assessed the fate of the core promoter recognition complex, TFIID, during skeletal myogenesis. Here we report that differentiation of myoblast to myotubes involves the disruption of the canonical holo-TFIID and replacement by a novel TRF3/TAF3 (TBP-related factor 3/TATA-binding protein-associated factor 3) complex. This required switching of core promoter complexes provides organisms a simple yet effective means to selectively turn on one transcriptional program while silencing many others. Although this drastic but parsimonious transcriptional switch had previously escaped our attention, it may represent a more general mechanism for regulating cell type-specific terminal differentiation.