Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA.
Development. 2014 May;141(10):2108-18. doi: 10.1242/dev.108118. Epub 2014 Apr 24.
Transcription factors and microRNAs (miRNAs) are two important classes of trans-regulators in differential gene expression. Transcription factors occupy cis-regulatory motifs in DNA to activate or repress gene transcription, whereas miRNAs specifically pair with seed sites in target mRNAs to trigger mRNA decay or inhibit translation. Dynamic spatiotemporal expression patterns of transcription factors and miRNAs during development point to their stage- and tissue-specific functions. Recent studies have focused on miRNA functions during development; however, much remains to explore regarding how the expression of miRNAs is initiated and how dynamic miRNA expression patterns are achieved by transcriptional regulatory networks at different developmental stages. Here, we focused on the identification, regulation and function of miRNAs during the earliest stage of Drosophila development, when the maternal-to-zygotic transition (MZT) takes place. Eleven miRNA clusters comprise the first set of miRNAs activated in the blastoderm embryo. The transcriptional activator Zelda is required for their proper activation and regulation, and Zelda binding observed in genome-wide binding profiles is predictive of enhancer activity. In addition, other blastoderm transcription factors, comprising both activators and repressors, the activities of which are potentiated and coordinated by Zelda, contribute to the accurate temporal and spatial expression of these miRNAs, which are known to function in diverse developmental processes. Although previous genetic studies showed no early phenotypes upon loss of individual miRNAs, our analysis of the miR-1; miR-9a double mutant revealed defects in gastrulation, demonstrating the importance of co-activation of miRNAs by Zelda during the MZT.
转录因子和 microRNAs（miRNAs）是差异基因表达中两种重要的转录调控因子。转录因子占据 DNA 中的顺式调控元件，激活或抑制基因转录，而 miRNAs 则特异性地与靶 mRNA 的种子位点结合，触发 mRNA 降解或抑制翻译。转录因子和 miRNAs 在发育过程中的动态时空表达模式表明它们具有阶段特异性和组织特异性功能。最近的研究集中在 miRNAs 在发育过程中的功能；然而，关于 miRNA 的表达是如何起始的，以及转录调控网络如何在不同的发育阶段实现动态 miRNA 表达模式，仍有许多需要探索。在这里，我们专注于鉴定、调控和功能的 miRNA 在果蝇发育的最早阶段，当母体到合子的过渡（MZT）发生时。十一个 miRNA 簇组成了第一个在胚胎胚层中激活的 miRNA 簇。转录激活因子 Zelda 是它们正确激活和调控所必需的，并且在全基因组结合图谱中观察到的 Zelda 结合预测了增强子活性。此外，其他胚层转录因子，包括激活子和抑制剂，它们的活性被 Zelda 增强和协调，有助于这些 miRNA 的准确时空表达，已知这些 miRNA 在不同的发育过程中发挥作用。尽管以前的遗传研究表明在单个 miRNA 缺失时没有早期表型，但我们对 miR-1；miR-9a 双突变体的分析显示在原肠胚形成过程中存在缺陷，这表明在 MZT 期间，Zelda 对 miRNAs 的共同激活在其中起着重要作用。
