Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Gene. 2011 Dec 1;489(1):55-62. doi: 10.1016/j.gene.2011.08.017. Epub 2011 Sep 5.
Expression of ribosomal proteins is controlled by the Target of Rapamycin (TOR) kinase. The Saccharomyces cerevisiae Forkhead-like transcription factor Fhl1 is important for this regulation, and its localization to ribosomal protein gene promoters requires the high mobility group protein HMO1. We show here that HMO1 expression is similarly controlled by TOR signaling. Reporter constructs in which lacZ is under control of the HMO1 promoter show that HMO1 promoter activity is repressed on inactivation of TOR and that HMO1 is required for this repression. Chromatin immunoprecipitation shows that Fhl1 localizes to the HMO1 promoter in an HMO1-dependent fashion and that it centers on a predicted Fhl1 site, and removal of the Fhl1 site in the HMO1 promoter attenuates the response to rapamycin. Taken together, our data show that the HMO1 promoter is regulated by TOR signaling, and that TOR can signal through an HMO1- and Fhl1-dependent mechanism, as proposed for TOR-mediated regulation of ribosomal protein expression. The shared mechanism of regulation further reinforces the central role of HMO1 in TOR-mediated regulation of ribosomal protein gene expression.
核糖体蛋白的表达受雷帕霉素靶蛋白（TOR）激酶的控制。酿酒酵母叉头样转录因子 Fhl1 对这种调节很重要，其定位于核糖体蛋白基因启动子需要高迁移率族蛋白 HMO1。我们在这里表明，HMO1 的表达也受到 TOR 信号的控制。在 HMO1 启动子控制下的 lacZ 报告构建体表明，TOR 失活时 HMO1 启动子活性受到抑制，并且 HMO1 是这种抑制所必需的。染色质免疫沉淀表明，Fhl1 以依赖 HMO1 的方式定位于 HMO1 启动子上，并且它集中在一个预测的 Fhl1 位点上，并且 HMO1 启动子中 Fhl1 位点的缺失减弱了对 rapamycin 的反应。总之，我们的数据表明 HMO1 启动子受 TOR 信号的调节，并且 TOR 可以通过 HMO1 和 Fhl1 依赖的机制发出信号，正如 TOR 介导的核糖体蛋白表达调节所提出的那样。共同的调节机制进一步加强了 HMO1 在 TOR 介导的核糖体蛋白基因表达调节中的核心作用。
