Universal promoter scanning by Pol II during transcription initiation in Saccharomyces cerevisiae
Universal promoter scanning by Pol II during transcription initiation in Saccharomyces cerevisiae
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DOI：
10.1186/s13059-020-02040-0
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发表时间：
2020-06-02
期刊：
影响因子：
12.3
通讯作者：
Kaplan, Craig D.
中科院分区：
文献类型：
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作者：
Qiu, Chenxi;Jin, Huiyan;Kaplan, Craig D.
背景大多数真核生物启动子利用多个转录起始点(Tsss)。对于大多数物种来说，如何在真核生物的单个启动子上指定多个TS尚不清楚。在酿酒酵母中，由Pol II和保守的通用转录因子(GTF)组成的预起始复合体(PIC)组装并打开TSS上游的DNA。来自模型启动者的证据表明，PIC从上游到下游扫描以识别TSS。先前的结果表明，当Pol II的催化活性或GTF功能发生变化时，TSS在扫描发生的启动子上的分布以极性方式移动。结果为了确定在酿酒酵母中跨启动子类别扫描启动子的程度，我们干扰了Pol II的催化活性和GTF功能，并分析了它们对全基因组TSS使用的影响。我们发现，POL II、TFIIB或TFIIF功能的改变广泛地改变了与所有酵母启动子的启动子扫描操作一致的起始区，而与启动子类别无关。然而，启动子结构可以通过扫描模型预测的方式确定启动子对POL II活性变化的敏感性程度。结论我们的观察结合以前的数据验证了Pol II在酵母中启动的扫描模型的关键预测，我们称之为射击库。在这个模型中，Pol II的催化活性、Pol II扫描的速度和过程以及启动子序列决定了TSS的分布和它们的使用。
Background The majority of eukaryotic promoters utilize multiple transcription start sites (TSSs). How multiple TSSs are specified at individual promoters across eukaryotes is not understood for most species. In Saccharomyces cerevisiae, a pre-initiation complex (PIC) comprised of Pol II and conserved general transcription factors (GTFs) assembles and opens DNA upstream of TSSs. Evidence from model promoters indicates that the PIC scans from upstream to downstream to identify TSSs. Prior results suggest that TSS distributions at promoters where scanning occurs shift in a polar fashion upon alteration in Pol II catalytic activity or GTF function. Results To determine the extent of promoter scanning across promoter classes in S. cerevisiae, we perturb Pol II catalytic activity and GTF function and analyze their effects on TSS usage genome-wide. We find that alterations to Pol II, TFIIB, or TFIIF function widely alter the initiation landscape consistent with promoter scanning operating at all yeast promoters, regardless of promoter class. Promoter architecture, however, can determine the extent of promoter sensitivity to altered Pol II activity in ways that are predicted by a scanning model. Conclusions Our observations coupled with previous data validate key predictions of the scanning model for Pol II initiation in yeast, which we term the shooting gallery. In this model, Pol II catalytic activity and the rate and processivity of Pol II scanning together with promoter sequence determine the distribution of TSSs and their usage.