de Jonge Wim J, O'Duibhir Eoghan, Lijnzaad Philip, van Leenen Dik, Groot Koerkamp Marian Ja, Kemmeren Patrick, Holstege Frank Cp
Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
EMBO J. 2017 Feb 1;36(3):274-290. doi: 10.15252/embj.201695621. Epub 2016 Dec 15.
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/TATA-like 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.
组成型表达的管家基因与调控基因之间经常存在重要区别。尽管通常由不同的DNA元件、染色质结构和辅因子来表征，但尚不清楚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些差异。我们表明，以SAGA为主导/TATA框的启动子对激活剂数量的变化更敏感，甚至与依赖相同激活剂Hsf1的TFIID/TATA样启动子相比也是如此。因此，可调控性是启动子类别的固有属性。进一步分析表明，SAGA/TATA框启动子更具动态性，因为通过SAGA招募的TATA结合蛋白容易被Mot1去除。此外，激活剂耗尽后核小体构型在SAGA/TATA框启动子上发生变化，似乎不太适合预起始复合物的形成。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：激活剂可以根据核心启动子类别引发不同的反应。
