Promoter DNA sequence guides factors that position the +1 nucleosome and facilitate TBP binding [array]

Here we present evidence that precise positioning of the +1 promoter nucleosome in yeast is critical for efficient TBP binding and pre-initiation complex assembly, and is determined, at least in part, by the action of two key factors, the essential chromatin remodeler RSC and one (or more) of a small set of ubiquitous pioneer transcription factors (PTFs). Despite their widespread co-localization, we show that RSC and PTFs often act independently to generate accessible chromatin. Furthermore, we present evidence that RSC binding, as well as the strength and directionality of its action on nucleosomes, depends upon the arrangement of two specific DNA motifs relative to nearby PTF binding sites. Our results provide insights into how promoter DNA sequence instructs trans-acting factors to precisely control nucleosome architecture and stimulate transcription initiation.本研究提供证据表明，酵母中+1号启动子核小体（+1 promoter nucleosome）的精确定位，对于高效结合TATA盒结合蛋白（TBP）以及组装预起始复合物（pre-initiation complex）至关重要，且该定位至少部分由两类关键因子的作用所决定：一是必需染色质重塑因子RSC，二是由少量通用先锋转录因子（PTFs）组成的小集合中的一个或多个成员。尽管RSC与PTFs广泛共定位，但本研究证实二者通常可独立发挥功能以形成可及染色质。此外，本研究还提供证据显示，RSC的结合特性，以及其对核小体作用的强度与方向性，均取决于两个特定DNA基序与邻近PTF结合位点的相对排布格局。本研究结果为启动子DNA序列如何指导反式作用因子精准调控核小体架构并促进转录起始提供了重要的科学见解。