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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >mef2 activity levels differentially affect gene expression during Drosophila muscle development
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mef2 activity levels differentially affect gene expression during Drosophila muscle development

机译：果蝇肌肉发育过程中，mef2活性水平差异影响基因表达

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摘要

Cell differentiation is controlled by key transcription factors, and a major question is how they orchestrate cell-type-specific genetic programs. Muscle differentiation is a well studied paradigm in which the conserved Mef2 transcription factor plays a pivotal role. Recent genomic studies have identified a large number of mef2-regulated target genes with distinct temporal expression profiles during Drosophila myogenesis. However, the question remains as to how a single transcription factor can control such diverse patterns of gene expression. In this study we used a strategy combining genomics and developmental genetics to address this issue in vivo during Drosophila muscle development. We found that groups of mef2-regulated genes respond differently to changes in mef2 activity levels: some require higher levels for their expression than others. Furthermore, this differential requirement correlates with when the gene is first expressed during the muscle differentiation program. Genes that require higher levels are activated later. These results implicate mef2 in the temporal regulation of muscle gene expression, and, consistent with this, we show that changes in mef2 activity levels can alter the start of gene expression in a predictable manner. Together these results indicate that Mef2 is not an all-or-none regulator; rather, its action is more subtle, and levels of its activity are important in the differential expression of muscle genes. This suggests a route by which mef2 can orchestrate the muscle differentiation program and contribute to the stringent regulation of gene expression during myogenesis.
机译：细胞分化由关键的转录因子控制，一个主要的问题是它们如何协调细胞类型特异性的遗传程序。肌肉分化是一个经过充分研究的范例，其中保守的Mef2转录因子起着关键作用。最近的基因组研究已确定了果蝇成肌过程中大量mef2调控的目标基因具有不同的时间表达谱。然而，关于单个转录因子如何能控制基因表达的这种多样模式的问题仍然存在。在这项研究中，我们使用了一种结合了基因组学和发育遗传学的策略来解决果蝇肌肉发育过程中的体内问题。我们发现，mef2调控基因组对mef2活性水平变化的反应不同：一些表达水平比其他表达水平更高。此外，该差异需求与基因在肌肉分化程序中首次表达的时间有关。需要更高水平的基因随后被激活。这些结果暗示了mef2在肌肉基因表达的时间调控中，与此一致的是，我们表明mef2活性水平的改变可以以可预测的方式改变基因表达的开始。这些结果加在一起表明，Mef2不是一个全有或全无的调节器。相反，它的作用更加微妙，其活性水平在肌肉基因的差异表达中也很重要。这暗示了mef2可以编排肌肉分化程序并有助于在成肌过程中严格调控基因表达的途径。

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