The Snail Repressor Inhibits Release, Not Elongation, of Paused Pol II in the Drosophila Embryo
The Snail Repressor Inhibits Release, Not Elongation, of Paused Pol II in the Drosophila Embryo
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DOI：
10.1016/j.cub.2011.08.019
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发表时间：
2011-09-27
期刊：
影响因子：
9.2
通讯作者：
Levine, Michael
中科院分区：
文献类型：
--
作者：
Bothma, Jacques P.;Magliocco, Joe;Levine, Michael
果蝇细胞前胚胎发育的特点是基因活性异常迅速的转变，广泛分布的母体调节梯度让位于受精后一小时窗口内基因表达的精确开/关模式[1]。转录抑制在这一过程中发挥了关键作用，在基因激活的广泛区域内描绘了尖锐的表达模式(例如，配对规则条纹)。多达20种不同的序列特异性抑制物参与了这一过程，然而它们抑制基因表达的机制仍然难以捉摸[2]。在这里，我们报告了一种转录抑制的定量可视化方法的发展。我们专注于蜗牛抑制因子，它建立了推测的中胚层和神经源性外胚层之间的边界[3]。我们发现，延长的POLII复合体在蜗牛抑制开始后完成转录。结果，中等大小的基因(例如，22kb的sog基因座)仅在数十分钟的抑制后才完全沉默。我们认为，这种“抑制滞后”对胚胎模式的调控动态施加了严重的限制，并进一步表明，转录后调控因子，如microRNAs，需要抑制在长时间的基因沉默期间产生的不想要的转录产物。
The development of the precellular Drosophila embryo is characterized by exceptionally rapid transitions in gene activity, with broadly distributed maternal regulatory gradients giving way to precise on/off patterns of gene expression within a one-hour window, between two and three hours after fertilization [1]. Transcriptional repression plays a pivotal role in this process, delineating sharp expression patterns (e.g., pair-rule stripes) within broad domains of gene activation. As many as 20 different sequence-specific repressors have been implicated in this process, yet the mechanisms by which they silence gene expression have remained elusive [2]. Here we report the development of a method for the quantitative visualization of transcriptional repression. We focus on the Snail repressor, which establishes the boundary between the presumptive mesoderm and neurogenic ectoderm [3]. We find that elongating Pol II complexes complete transcription after the onset of Snail repression. As a result, moderately sized genes (e.g., the 22 kb sog locus) are fully silenced only after tens of minutes of repression. We propose that this "repression lag" imposes a severe constraint on the regulatory dynamics of embryonic patterning and further suggest that posttranscriptional regulators, like microRNAs, are required to inhibit unwanted transcripts produced during protracted periods of gene silencing.