Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Cell. 2010 Nov 12;143(4):540-51. doi: 10.1016/j.cell.2010.10.004.
Metazoan transcription is controlled through either coordinated recruitment of transcription machinery to the gene promoter or 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.
真核生物转录是通过转录机制在基因启动子处的协调募集或 RNA 聚合酶 II（Pol II）在早期延伸过程中的调节暂停来控制的。我们报告说，使用这些不同调控策略的基因之间存在一个显著的差异，这在于它们的 DNA 序列所指定的“默认”染色质结构。Pol II 暂停在高度调控的基因中很明显，这些基因的序列内在地不利于基因内核小体的形成，但有利于核小体对启动子的阻断。相比之下，缺乏明显的 Pol II 暂停的管家基因在下游显示出更高的核小体占有率，但无论聚合酶结合如何，它们的启动子都没有核小体。我们的结果表明，暂停的 Pol II 的一个关键作用是与核小体竞争高度调控的启动子的占有率，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。
