Transcription factor binding to target sites in vivo is a dynamic process that involves cycles of association and dissociation, with individual proteins differing in their binding dynamics. The dynamics at individual sites on a genomic scale have been investigated in yeast cells, but comparable experiments have not been done in multicellular eukaryotes. Here, we describe a tamoxifen-inducible, time-course ChIP-seq approach to measure transcription factor binding dynamics at target sites throughout the human genome. As observed in yeast cells, the TATA-binding protein (TBP) typically displays rapid turnover at RNA polymerase (Pol) II-transcribed promoters, slow turnover at Pol III promoters, and very slow turnover at the Pol I promoter. Turnover rates vary widely among Pol II promoters in a manner that does not correlate with the level of TBP occupancy. Human Pol II promoters with slow TBP dissociation preferentially contain a TATA consensus motif, support high transcriptional activity of downstream genes, and are linked with specific activators and chromatin remodelers. These properties of human promoters with slow TBP turnover differ from those of yeast promoters with slow turnover. These observations suggest that TBP binding dynamics differentially affect promoter function and gene expression, possibly at the level of transcriptional reinitiation/bursting.

中文翻译：

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TATA 结合蛋白与人类基因组关联的启动子特异性动力学。

转录因子与体内靶位点的结合是一个动态过程，涉及结合和解离的循环，单个蛋白质的结合动力学不同。已经在酵母细胞中研究了基因组规模上各个位点的动力学，但尚未在多细胞真核生物中进行类似的实验。在这里，我们描述了一种他莫昔芬诱导的时程 ChIP-seq 方法来测量整个人类基因组目标位点的转录因子结合动力学。正如在酵母细胞中观察到的那样，TATA 结合蛋白 (TBP) 通常在 RNA 聚合酶 (Pol) II 转录启动子处显示快速转换，在 Pol III 启动子处显示缓慢转换，而在 Pol I 启动子处显示非常缓慢的转换。Pol II 发起人的离职率差异很大，其方式与 TBP 入住率水平无关。具有缓慢 TBP 解离的人 Pol II 启动子优先包含 TATA 共有基序，支持下游基因的高转录活性，并与特异性激活剂和染色质重塑剂相关。具有缓慢 TBP 转换的人类启动子的这些特性不同于具有缓慢转换的酵母启动子。这些观察结果表明，TBP 结合动力学对启动子功能和基因表达有不同的影响，可能在转录重新启动/爆发的水平上。并与特定的激活剂和染色质重塑剂相关联。具有缓慢 TBP 转换的人类启动子的这些特性不同于具有缓慢转换的酵母启动子。这些观察结果表明，TBP 结合动力学对启动子功能和基因表达有不同的影响，可能在转录重新启动/爆发的水平上。并与特定的激活剂和染色质重塑剂相关联。具有缓慢 TBP 转换的人类启动子的这些特性不同于具有缓慢转换的酵母启动子。这些观察结果表明，TBP 结合动力学对启动子功能和基因表达有不同的影响，可能在转录重新启动/爆发的水平上。