Drosophila MEF2 is a direct regulator of Actin57B transcription in cardiac, skeletal, and visceral muscle lineages
Drosophila MEF2 is a direct regulator of Actin57B transcription in cardiac, skeletal, and visceral muscle lineages
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DOI：
10.1016/s0925-4773(01)00586-x
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发表时间：
2002-01-01
影响因子：
2.6
通讯作者：
Cripps, RM
中科院分区：
文献类型：
--
作者：
Kelly, KK;Meadows, SM;Cripps, RM
为了确定在肌肉发生过程中发生的调控事件，我们表征了果蝇黑腹肌动蛋白基因肌动蛋白57B的转录调控。Act57B转录最先在内脏肌肉前体中检测到，在胚胎发育结束时在所有胚胎肌肉中都能检测到。通过缺失分析，我们确定了一个595bp的启动子元件，足以在所有三个肌肉谱系中高水平表达。该片段含有一个在黑腹果蝇和果蝇之间保守的MEF2结合位点，可与胚胎核提取液中的MEF2蛋白结合。MEF2位点突变严重降低了胚胎中启动子的活性，在MEF2突变体中，Act57B的表达严重降低，表明MEF2是Act57B的重要调控因子。我们还表明，MEF2可能与结合在595bp元件内的额外序列的因子协同作用。这些发现强调了MEF2在控制所有肌肉系分化中的重要性。我们的实验揭示了结构基因的一种新的调节机制，其中所有胚胎肌肉中的高水平表达是通过单个转录因子结合位点来调节的。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
To identify regulatory events occurring during myogenesis, we characterized the transcriptional regulation of a Drosophila melanogaster actin gene, Actin 57B. Act57B transcription is first detected in visceral muscle precursors and is detectable in all embryonic muscles by the end of embryogenesis. Through deletion analysis we identified a 595 bp promoter element that was sufficient for high levels of expression in all three muscle lineages. This fragment contained a MEF2 binding site conserved between D. melanogaster and Drosophila virilis which bound MEF2 protein in embryo nuclear extracts. Mutation of the MEF2 site severely reduced promoter activity in embryos, and in Mef2 mutants Act57B expression was severely decreased, demonstrating MEF2 is an essential regulator of Act57B. We also showed that MEF2 likely acts synergistically with factors bound to additional sequences within the 595 bp element. These findings underline the importance of MEF2 in controlling differentiation in all muscle lineages. Our experiments reveal a novel regulatory mechanism for a structural gene where high levels of expression in all embryonic muscles is regulated through a single transcription factor binding site. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.