Control of transcriptional pausing by biased thermal fluctuations on repetitive genomic sequences
Control of transcriptional pausing by biased thermal fluctuations on repetitive genomic sequences
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DOI：
10.1073/pnas.1607760113
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发表时间：
2016-11-22
影响因子：
11.1
通讯作者：
Lukatsky, David B.
中科院分区：
文献类型：
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作者：
Imashimizu, Masahiko;Afek, Ariel;Lukatsky, David B.
在转录延伸的过程中，RNA聚合酶（RNAP）在基因组DNA的高度非随机位置暂停，广泛调节转录;然而，负责识别这种暂停位置的分子机制仍然知之甚少。在这里，使用统计力学建模和高通量测序和生化数据的组合，我们评估热波动对RNAP暂停调节的影响。我们证明了RNAP的扩散回溯，这是有偏见的重复DNA序列元素，导致转录暂停。这种效应源于伸长复合体的微观异质性增加，因此是熵支配的。这份报告显示了基因组中编码的重复序列元件与热波动驱动的RNAP暂停调节之间的联系。
In the process of transcription elongation, RNA polymerase (RNAP) pauses at highly nonrandom positions across genomic DNA, broadly regulating transcription; however, molecular mechanisms responsible for the recognition of such pausing positions remain poorly understood. Here, using a combination of statistical mechanical modeling and high-throughput sequencing and biochemical data, we evaluate the effect of thermal fluctuations on the regulation of RNAP pausing. We demonstrate that diffusive backtracking of RNAP, which is biased by repetitive DNA sequence elements, causes transcriptional pausing. This effect stems from the increased microscopic heterogeneity of an elongation complex, and thus is entropydominated. This report shows a linkage between repetitive sequence elements encoded in the genome and regulation of RNAP pausing driven by thermal fluctuations.