Mot1 activates and represses transcription by direct, ATPase-dependent mechanisms

Mot1 activates and represses transcription by direct, ATPase-dependent mechanisms
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DOI:
10.1073/pnas.052397899
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发表时间:
2002-03-05
影响因子:
11.1
通讯作者:
Auble, DT
Auble, DT
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Dasgupta, A;Darst, RP;Auble, DT

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Mot1 是一种必需的酵母 Snf2/Swi2 相关 ATP 酶,对基因表达具有积极和消极的影响。在体外,Mot1 可以在 ATP 依赖性反应中破坏 TATA 结合蛋白-DNA 复合物。这种活性可以解释 Mot1 介导的转录抑制,但 Mot1 如何激活转录尚不清楚。值得注意的是,我们证明 Mot1 在体内定位于 Mot1 抑制基因和 Mot1 激活基因的启动子。此外,Mot1 ATPase 活性对于基因活性的激活和抑制都是必需的。这些发现表明 Mot1 ATP 酶在激活基因上具有新功能,可能涉及 ATP 驱动的前起始复合物重组。 Mot1 调节在丰富培养基中生长的细胞中大约 3% 的酵母基因的表达。大多数这些基因都被 Mot1 抑制,这与 Mot1 的 ATP 依赖性 TATA 结合蛋白-DNA 解离活性一致。此外,大约 77% 的 Mot1 抑制基因参与双轴转变、应激反应、交配或孢子形成。 NC2 和 Srb10 控制的基因组与 Mot1 控制的基因组密切相关,表明这些因子在全球范围内协同参与转录控制。
Mot1 is an essential yeast Snf2/Swi2-related ATPase that exerts both positive and negative effects on gene expression. In vitro, Mot1 can disrupt TATA-binding protein-DNA complexes in an ATP-dependent reaction. This activity can explain Mot1-mediated transcriptional repression, but how Mot1 activates transcription is unknown. We demonstrate that, remarkably, Mot1 is localized in vivo to promoters for both Mot1-repressed and Mot1-activated genes. Moreover, Mot1 ATPase activity is required for both activation and repression of gene activity. These findings suggest a novel function for the Mot1 ATPase at activated genes, perhaps involving ATP-driven reorganization of the preinitiation complex. Mot1 regulates the expression of approximate to3% of yeast genes in cells grown in rich medium. Most of these genes are repressed by Mot1, consistent with Mot1's ATP-dependent TATA-binding protein-DNA dissociating activity. Additionally, approximate to77% of the Mot1-repressed genes are involved in the diauxic shift, stress response, mating, or sporulation. The gene sets controlled by NC2 and Srb10 are strongly correlated with the Mot1-controlled set, suggesting that these factors cooperate in transcriptional control on a global scale.