Precise developmental gene expression arises from globally stochastic transcriptional activity.
Precise developmental gene expression arises from globally stochastic transcriptional activity.
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DOI：
10.1016/j.cell.2013.07.025
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发表时间：
2013-08-15
期刊：
影响因子：
64.5
通讯作者：
Gregor T
中科院分区：
文献类型：
--
作者：
Little SC;Tikhonov M;Gregor T
早期的胚胎模式事件是惊人的精确。潜在的分子细节是难以捉摸的，似乎与在整个门观察到的随机基因表达不兼容。利用果蝇胚胎中的单分子mRNA定量，我们确定了四个关键模式基因表达的波动幅度。MRNAs的积累在不同基因之间是相同的，并在相邻的核之间波动~8%，以产生精确的蛋白质分布。相反，转录基因座表现出约45%的内在噪声，与特定的启动子-增强子结构或波动的输入无关。胚胎通过直截了当的时空平均恢复精确的转录分布，而不需要调节反馈。基因之间共有的共同表达特征表明，基本物理限制的噪声主导了即时转录读出的波动。
Early embryonic patterning events are strikingly precise. The underlying molecular details are elusive and appear incompatible with stochastic gene expression observed across phyla. Using single molecule mRNA quantification in Drosophila embryos, we determine the magnitude of fluctuations in the expression of four critical patterning genes. The accumulation of mRNAs is identical across genes and fluctuates by ~8% between neighboring nuclei to generate precise protein distributions. In contrast, transcribing loci exhibit an intrinsic noise of ~45% independent of specific promoter-enhancer architecture or fluctuating inputs. The embryo recovers precise transcript distribution through straightforward spatiotemporal averaging without regulatory feedback. The common expression characteristics shared between genes suggest that the noise of fundamental physical constraints dominates the fluctuations of immediate transcriptional readout.
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