Muse Ginger W, Gilchrist Daniel A, Nechaev Sergei, Shah Ruchir, Parker Joel S, Grissom Sherry F, Zeitlinger Julia, Adelman Karen
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Nat Genet. 2007 Dec;39(12):1507-11. doi: 10.1038/ng.2007.21. Epub 2007 Nov 11.
Regulation of gene expression is integral to the development and survival of all organisms. Transcription begins with the assembly of a pre-initiation complex at the gene promoter, followed by initiation of RNA synthesis and the transition to productive elongation. In many cases, recruitment of RNA polymerase II (Pol II) to a promoter is necessary and sufficient for activation of genes. However, there are a few notable exceptions to this paradigm, including heat shock genes and several proto-oncogenes, whose expression is attenuated by regulated stalling of polymerase elongation within the promoter-proximal region. To determine the importance of polymerase stalling for transcription regulation, we carried out a genome-wide search for Drosophila melanogaster genes with Pol II stalled within the promoter-proximal region. Our data show that stalling is widespread, occurring at hundreds of genes that respond to stimuli and developmental signals. This finding indicates a role for regulation of polymerase elongation in the transcriptional responses to dynamic environmental and developmental cues.
基因表达调控是所有生物体发育和生存所不可或缺的。转录始于在基因启动子处组装前起始复合物,随后启动RNA合成并过渡到有效的延伸阶段。在许多情况下,将RNA聚合酶II(Pol II)招募到启动子对于基因激活是必要且充分的。然而,这种模式存在一些显著的例外情况,包括热休克基因和一些原癌基因,其表达因启动子近端区域内聚合酶延伸的调控性停滞而减弱。为了确定聚合酶停滞对转录调控的重要性,我们在全基因组范围内搜索了黑腹果蝇中在启动子近端区域存在Pol II停滞的基因。我们的数据表明,停滞现象很普遍,发生在数百个对刺激和发育信号有反应的基因上。这一发现表明聚合酶延伸调控在对动态环境和发育线索的转录反应中发挥作用。