Laboratory of Molecular Genetics, Wadsworth Center, New York State Department of Health, Albany, NY 12201-0509, USA.
EMBO J. 2012 Jan 4;31(1):44-57. doi: 10.1038/emboj.2011.362. Epub 2011 Oct 4.
The evolutionarily conserved Mediator complex is required for transcription of nearly all RNA Pol II-dependent promoters, with the tail module serving to recruit Mediator to active promoters in current models. However, transcriptional dependence on tail module subunits varies in a gene-specific manner, and the generality of the tail module requirement for transcriptional activation has not been explored. Here, we show that tail module subunits function redundantly to recruit Mediator to promoters in yeast, and transcriptome analysis shows stronger effects on genome-wide expression in a double-tail subunit deletion mutant than in single-subunit deletion mutants. Unexpectedly, TATA-containing and SAGA-dependent genes were much more affected by impairment of tail module function than were TFIID-dependent genes. Consistent with this finding, Mediator and preinitiation complex association with SAGA-dependent promoters is substantially reduced in gal11/med15Δ med3Δ yeast, whereas association of TBP, Pol II, and other Mediator modules with TFIID-dependent genes is largely independent of the tail module. Thus, we have identified a connection between the Mediator tail module and the division of promoter dependence between TFIID and SAGA.
进化上保守的 Mediator 复合物对于几乎所有 RNA Pol II 依赖性启动子的转录都是必需的，在当前模型中，尾部模块用于将 Mediator 募集到活性启动子上。然而，尾部模块亚基对转录的依赖性在基因特异性上存在差异，并且尾部模块对于转录激活的普遍性尚未得到探索。在这里，我们表明尾部模块亚基在酵母中以冗余的方式募集 Mediator 到启动子上，并且转录组分析显示在双尾部亚基缺失突变体中对全基因组表达的影响比在单个亚基缺失突变体中更强。出乎意料的是，与 TFIID 依赖性基因相比，含有 TATA 框和 SAGA 依赖性基因的基因受到尾部模块功能障碍的影响更大。与这一发现一致的是，在 gal11/med15Δ med3Δ 酵母中，与 SAGA 依赖性启动子相关的 Mediator 和起始前复合物的结合大大减少，而 TBP、Pol II 和其他 Mediator 模块与 TFIID 依赖性基因的结合在很大程度上独立于尾部模块。因此，我们已经确定了 Mediator 尾部模块与 TFIID 和 SAGA 之间启动子依赖性的划分之间的联系。
