A multiscale investigation of bicoid-dependent transcriptional events in Drosophila embryos.
A multiscale investigation of bicoid-dependent transcriptional events in Drosophila embryos.
复制标题
DOI：
10.1371/journal.pone.0019122
复制
发表时间：
2011-04-22
期刊：
影响因子：
3.7
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
He F;Ren J;Wang W;Ma J
形态发生素分子形成浓度梯度，为发育中的胚胎中的细胞提供空间信息。细胞究竟如何解码这些信息以形成具有清晰边界的模式仍然是一个悬而未决的问题。例如，果蝇形态发生蛋白 Bicoid (Bcd) 在激活其靶基因以在发育过程中建立清晰的表达边界方面是否发挥短暂或持续的作用仍然存在争议。在这项研究中，我们描述了一种同时检测发育胚胎中 Bcd 及其靶基因新生转录本的方法。这种方法使我们能够在不同的尺度上研究 Bcd 与其靶基因的单个拷贝的转录状态之间的关系。我们发现，在同时分析的三个尺度上——胚胎、细胞核和局部，活跃转录的基因拷贝与高 Bcd 浓度相关。这些结果强调了 Bcd 作为其靶基因个体拷贝在发育过程中转录决策的持续输入的重要性。我们还表明，Bcd 依赖性转录决策的噪声明显高于 Bcd 依赖性基因产物，这表明，与理论研究一致，时间和/或空间平均降低了 Bcd 激活转录输出的噪声。最后，我们对 X 连锁 Bcd 靶基因的分析表明，Bcd 依赖性转录在雄性中的爆发频率是雌性中的两倍，这为早期果蝇胚胎中的剂量补偿提供了机制。我们的研究首次通过实验揭示了 Bcd 在控制实际转录事件中的作用，同时其位置信息在发育过程中被解码。它确立了 Bcd 在其靶基因的各个拷贝的转录决策中的持续作用，以产生清晰的表达边界。它还提供了时间和/或空间平均对 Bcd 依赖性转录输出的影响的实验评估，并在早期果蝇胚胎中建立了剂量补偿机制。
Morphogen molecules form concentration gradients to provide spatial information to cells in a developing embryo. Precisely how cells decode such information to form patterns with sharp boundaries remains an open question. For example, it remains controversial whether the Drosophila morphogenetic protein Bicoid (Bcd) plays a transient or sustained role in activating its target genes to establish sharp expression boundaries during development. In this study, we describe a method to simultaneously detect Bcd and the nascent transcripts of its target genes in developing embryos. This method allows us to investigate the relationship between Bcd and the transcriptional status of individual copies of its target genes on distinct scales. We show that, on three scales analyzed concurrently—embryonic, nuclear and local, the actively-transcribing gene copies are associated with high Bcd concentrations. These results underscore the importance of Bcd as a sustained input for transcriptional decisions of individual copies of its target genes during development. We also show that the Bcd-dependent transcriptional decisions have a significantly higher noise than Bcd-dependent gene products, suggesting that, consistent with theoretical studies, time and/or space averaging reduces the noise of Bcd-activated transcriptional output. Finally, our analysis of an X-linked Bcd target gene reveals that Bcd-dependent transcription bursts at twice the frequency in males as in females, providing a mechanism for dosage compensation in early Drosophila embryos. Our study represents a first experimental uncovering of the actions of Bcd in controlling the actual transcriptional events while its positional information is decoded during development. It establishes a sustained role of Bcd in transcriptional decisions of individual copies of its target genes to generate sharp expression boundaries. It also provides an experimental evaluation of the effect of time and/or space averaging on Bcd-dependent transcriptional output, and establishes a dosage compensation mechanism in early Drosophila embryos.
登录
查看更多内容
影响因子：
3.4
作者：
He, Feng;Saunders, Timothy E.;Ma, Jun
通讯作者：
Ma, Jun
影响因子：
8.6
作者：
Erdmann, Thorsten;Howard, Martin;ten Wolde, Pieter Rein
通讯作者：
ten Wolde, Pieter Rein
影响因子：
--
作者：
He F;Wen Y;Cheung D;Deng J;Lu LJ;Jiao R;Ma J
通讯作者：
Ma J
影响因子：
64.8
作者：
JACKLE, H;TAUTZ, D;LEHMANN, R
通讯作者：
LEHMANN, R
影响因子：
64.5
作者：
DRIEVER, W;NUSSLEINVOLHARD, C
通讯作者：
NUSSLEINVOLHARD, C