Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation.

Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation.
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DOI:
10.1016/j.cell.2010.10.004
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发表时间:
2010-11-12
期刊:
影响因子:
64.5
通讯作者:
Adelman K
Adelman K
中科院分区:
生物学1区
文献类型:
--
作者:
Gilchrist DA;Dos Santos G;Fargo DC;Xie B;Gao Y;Li L;Adelman K

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后生动物的转录是通过协调募集的转录机器的基因启动子,或通过RNA聚合酶II(Pol II)在早期延长的调节暂停控制。我们报告说,使用这些不同的调控策略的基因之间的显着差异在于由其DNA序列指定的“默认”染色质结构。Pol II暂停在高度调控的基因中是突出的,其序列固有地不利于基因内的核小体形成,但有利于核小体对启动子的封闭。相比之下,管家基因,缺乏显着的Pol II暂停显示较高的核小体占用下游,但它们的启动子被剥夺的核小体,无论聚合酶结合。我们的研究结果表明,暂停Pol II的一个关键作用是与核小体竞争高度调节的启动子的占用,从而防止形成抑制性染色质结构,以促进进一步或未来的基因激活。
Metazoan transcription is controlled either through coordinated recruitment of transcription machinery to the gene promoter, or through regulated pausing of RNA polymerase II (Pol II) in early elongation. We report that a striking difference between genes that use these distinct regulatory strategies lies in the “default” chromatin architecture specified by their DNA sequences. Pol II pausing is prominent at highly-regulated genes whose sequences inherently disfavor nucleosome formation within the gene, but favor occlusion of the promoter by nucleosomes. In contrast, housekeeping genes that lack pronounced Pol II pausing show higher nucleosome occupancy downstream, but their promoters are deprived of nucleosomes regardless of polymerase binding. Our results indicate that a key role of paused Pol II is to compete with nucleosomes for occupancy of highly-regulated promoters, thereby preventing the formation of repressive chromatin architecture to facilitate further or future gene activation.
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