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转录因子活性的时间图谱:mef2在肌肉发育的所有阶段直接调控靶基因。

A temporal map of transcription factor activity: mef2 directly regulates target genes at all stages of muscle development.

作者信息

Sandmann Thomas, Jensen Lars J, Jakobsen Janus S, Karzynski Michal M, Eichenlaub Michael P, Bork Peer, Furlong Eileen E M

机构信息

European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.

出版信息

Dev Cell. 2006 Jun;10(6):797-807. doi: 10.1016/j.devcel.2006.04.009.

Abstract

Dissecting components of key transcriptional networks is essential for understanding complex developmental processes and phenotypes. Genetic studies have highlighted the role of members of the Mef2 family of transcription factors as essential regulators in myogenesis from flies to man. To understand how these transcription factors control diverse processes in muscle development, we have combined chromatin immunoprecipitation analysis with gene expression profiling to obtain a temporal map of Mef2 activity during Drosophila embryonic development. This global approach revealed three temporal patterns of Mef2 enhancer binding, providing a glimpse of dynamic enhancer use within the context of a developing embryo. Our results provide mechanistic insight into the regulation of Mef2's activity at the level of DNA binding and suggest cooperativity with the bHLH protein Twist. The number and diversity of new direct target genes indicates a much broader role for Mef2, at all stages of myogenesis, than previously anticipated.

摘要

剖析关键转录网络的组成部分对于理解复杂的发育过程和表型至关重要。遗传学研究强调了转录因子Mef2家族成员在从果蝇到人类的肌肉生成中作为重要调节因子的作用。为了了解这些转录因子如何控制肌肉发育中的各种过程,我们将染色质免疫沉淀分析与基因表达谱分析相结合,以获得果蝇胚胎发育过程中Mef2活性的时间图谱。这种全局方法揭示了Mef2增强子结合的三种时间模式,让我们得以一窥发育胚胎背景下动态增强子的使用情况。我们的结果为Mef2在DNA结合水平上的活性调节提供了机制性见解,并表明其与bHLH蛋白Twist存在协同作用。新的直接靶基因的数量和多样性表明,Mef2在肌肉生成的所有阶段所起的作用比之前预期的要广泛得多。

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