Department of Molecular Biology and Institute of Genetics and Genomics of Geneva (iGE3), Geneva, Switzerland.
Institut Jacques Monod, CNRS-Université Paris Diderot, Paris, France.
Nat Struct Mol Biol. 2019 Aug;26(8):744-754. doi: 10.1038/s41594-019-0273-3. Epub 2019 Aug 5.
Precise nucleosome organization at eukaryotic promoters is thought to be generated by multiple chromatin remodeler (CR) enzymes and to affect transcription initiation. Using an integrated analysis of chromatin remodeler binding and nucleosome occupancy following rapid remodeler depletion, we investigated the interplay between these enzymes and their impact on transcription in yeast. We show that many promoters are affected by multiple CRs that operate in concert or in opposition to position the key transcription start site (TSS)-associated +1 nucleosome. We also show that nucleosome movement after CR inactivation usually results from the activity of another CR and that in the absence of any remodeling activity, +1 nucleosomes largely maintain their positions. Finally, we present functional assays suggesting that +1 nucleosome positioning often reflects a trade-off between maximizing RNA polymerase recruitment and minimizing transcription initiation at incorrect sites. Our results provide a detailed picture of fundamental mechanisms linking promoter nucleosome architecture to transcription initiation.
真核生物启动子处精确的核小体组织被认为是由多种染色质重塑酶（CR）产生的，并且会影响转录起始。我们通过快速耗尽重塑酶后结合染色质重塑酶结合和核小体占有率的综合分析，研究了这些酶之间的相互作用及其对酵母转录的影响。我们表明，许多启动子受到多种 CR 的影响，这些 CR 协同或相反地作用以定位关键转录起始位点（TSS）相关的+1 核小体。我们还表明，CR 失活后核小体的移动通常是由另一个 CR 的活性引起的，并且在没有任何重塑活性的情况下，+1 核小体在很大程度上保持其位置。最后，我们提出了功能测定，表明+1 核小体定位通常反映了在最大程度地招募 RNA 聚合酶和最小化在错误位置起始转录之间的权衡。我们的结果提供了一个详细的画面，说明了将启动子核小体结构与转录起始联系起来的基本机制。
