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Mot1 Redistributes TBP from TATA-Containing to TATA-Less Promoters

机译:Mot1将TBP从包含TATA的分销商重新分配给了TATA-Less的启动子

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The Swi2/Snf2 family ATPase Mot1 displaces TATA-binding protein (TBP) from DNA in vitro, but the global relationship between Mot1 and TBP in vivo is unclear. In particular, how Mot1 activates transcription is poorly understood. To address these issues, we mapped the distribution of Mot1 and TBP on native chromatin at base pair resolution. Mot1 and TBP binding sites coincide throughout the genome, and depletion of TBP results in a global decrease in Mot1 binding. We find evidence that Mot1 approaches TBP from the upstream direction, consistent with its in vitro mode of action. Strikingly, inactivation of Mot1 leads to both increases and decreases in TBP-genome association. Sites of TBP gain tend to contain robust TATA boxes, while sites of TBP loss contain poly(dA-dT) tracts that may contribute to nucleosome exclusion. Sites of TBP gain are associated with increased gene expression, while decreased TBP binding is associated with reduced gene expression. We propose that the action of Mot1 is required to clear TBP from intrinsically preferred (TATA-containing) binding sites, ensuring sufficient soluble TBP to bind intrinsically disfavored (TATA-less) sites.
机译:Swi2 / Snf2家族的ATPase Mot1取代了体外DNA 中的TATA结合蛋白(TBP),但目前还不清楚Mot1与TBP 体内之间的整体关系。特别是,Mot1如何激活转录的了解很少。为了解决这些问题,我们将Mot1和TBP的分布在碱基对分辨率的天然染色质上作图。 Mot1和TBP结合位点在整个基因组中重合,而TBP的耗尽导致Mot1结合的整体降低。我们发现证据表明Mot1从上游方向接近TBP,与其体外作用方式一致。令人惊讶的是,Mot1的失活导致TBP基因组关联的增加和减少。 TBP丢失的位点倾向于包含坚固的TATA盒,而TBP丢失的位点包含可能有助于核小体排除的多聚(dA-dT)片段。 TBP获得位点与基因表达增加有关,而TBP结合减少与基因表达减少有关。我们建议需要Mot1的作用才能从本质上优先的(含TATA的)结合位点清除TBP,确保有足够的可溶性TBP结合固有的不利(无TATA的)位点。

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