Genome-wide dynamic nascent transcript profiles reveal that most paused RNA polymerases terminate

全基因组动态新生转录本谱分析表明,大多数暂停的RNA聚合酶会终止反应。

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Abstract

We present a simple model for analyzing and interpreting data from kinetic experiments that measure engaged RNA polymerase occupancy. The framework represents the densities of nascent transcripts within the pause region and the gene body as steady-state values determined by four key transcriptional processes: initiation, pause release, premature termination, and elongation. We validate the model's predictions using data from experiments that rapidly inhibit initiation and pause release. The model successfully classified factors based on the steps in early transcription that they regulate, confirming TBP and ZNF143 as initiation factors and heat shock factor and glucocorticoid receptor as pause release factors. We found that most paused polymerases terminate and paused polymerases are short-lived with half lives less than a minute. We make this model available as software to serve as a quantitative tool for determining the kinetic mechanisms of transcriptional regulation.

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