Tachibana Christine, Biddick Rhiannon, Law G Lynn, Young Elton T
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
J Biol Chem. 2007 Dec 28;282(52):37308-15. doi: 10.1074/jbc.M707363200. Epub 2007 Oct 31.
Snf1, the yeast AMP kinase homolog, is essential for derepression of glucose-repressed genes that are activated by Adr1. Although required for Adr1 DNA binding, the precise role of Snf1 is unknown. Deletion of histone deacetylase genes allowed constitutive promoter binding of Adr1 and Cat8, another activator of glucose-repressed genes. In repressed conditions, at the Adr1-and Cat8-dependent ADH2 promoter, partial chromatin remodeling had occurred, and the activators recruited a partial preinitiation complex that included RNA polymerase II. Transcription did not occur, however, unless Snf1 was activated, suggesting a Snf1-dependent event that occurs after RNA polymerase II recruitment. Glucose regulation persisted because shifting to low glucose increased expression. Glucose repression could be completely relieved by combining the three elements of 1) chromatin perturbation by mutation of histone deacetylases, 2) activation of Snf1, and 3) the addition of an Adr1 mutant that by itself confers only weak constitutive activity.
Snf1是酵母中AMP激酶的同源物，对于解除由Adr1激活的葡萄糖抑制基因的阻遏至关重要。尽管Snf1是Adr1与DNA结合所必需的，但其确切作用尚不清楚。组蛋白去乙酰化酶基因的缺失使得Adr1和Cat8（另一种葡萄糖抑制基因的激活剂）能够组成型地结合启动子。在阻遏条件下，在Adr1和Cat8依赖的ADH2启动子处，已经发生了部分染色质重塑，激活剂招募了一个包括RNA聚合酶II的部分预起始复合物。然而，除非Snf1被激活，转录不会发生，这表明在RNA聚合酶II招募后发生了一个依赖Snf1的事件。葡萄糖调节持续存在，因为转移到低糖环境会增加表达。通过结合以下三个要素可以完全解除葡萄糖阻遏：1）通过组蛋白去乙酰化酶突变进行染色质扰动，2）激活Snf1，3）添加一种自身仅具有弱组成型活性的Adr1突变体。
