Molecular mechanisms that distinguish TFIID housekeeping from regulatable SAGA promoters
Molecular mechanisms that distinguish TFIID housekeeping from regulatable SAGA promoters
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DOI：
10.15252/embj.201695621
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发表时间：
2017-02-01
期刊：
影响因子：
11.4
通讯作者：
Holstege, Frank C. P.
中科院分区：
文献类型：
--
作者：
de Jonge, Wim J.;O'Duibhir, Eoghan;Holstege, Frank C. P.
组成型表达的管家基因与受调控基因之间经常有一个重要的区别。虽然通常以不同的DNA元件、染色质结构和辅因子为特征，但不知道启动子类别在多大程度上严格遵循可调控性规则以及哪些分子机制决定了这种差异。我们发现，SAGA主导/TATA盒启动子更响应于激活剂的量的变化，甚至相比TFIID/TATA样启动子，依赖于相同的激活剂Hsf 1。因此，可调节性是启动子类的固有性质。进一步的分析表明，佐贺/TATA盒启动子是更动态的，因为通过佐贺的TATA结合蛋白的招聘是容易被Mot 1删除。此外，核小体配置激活剂耗尽后转移的佐贺/TATA盒启动子，似乎不太适合preinitiation复合物的形成。这些结果解释了管家基因和可调控基因之间的根本差异，揭示了组合控制的另一个方面：激活剂可以引起依赖于核心启动子类别的不同反应。
An important distinction is frequently made between constitutively expressed housekeeping genes versus regulated genes. Although generally characterized by different DNA elements, chromatin architecture and cofactors, it is not known to what degree promoter classes strictly follow regulatability rules and which molecular mechanisms dictate such differences. We show that SAGA-dominated/TATA-box promoters are more responsive to changes in the amount of activator, even compared to TFIID/TATAlike promoters that depend on the same activator Hsf1. Regulatability is therefore an inherent property of promoter class. Further analyses show that SAGA/TATA-box promoters are more dynamic because TATA-binding protein recruitment through SAGA is susceptible to removal by Mot1. In addition, the nucleosome configuration upon activator depletion shifts on SAGA/TATA-box promoters and seems less amenable to preinitiation complex formation. The results explain the fundamental difference between housekeeping and regulatable genes, revealing an additional facet of combinatorial control: an activator can elicit a different response dependent on core promoter class.