mef2c is activated directly by myogenic basic helix-loop-helix proteins during skeletal muscle development in vivo
mef2c is activated directly by myogenic basic helix-loop-helix proteins during skeletal muscle development in vivo
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DOI：
10.1016/s0925-4773(03)00178-3
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发表时间：
2003-09-01
影响因子：
2.6
通讯作者：
Black, BL
中科院分区：
文献类型：
--
作者：
Dodou, E;Xu, SM;Black, BL
骨骼肌发育需要众多转录因子的协同表达，以控制中胚层祖细胞向肌细胞命运的特化，以及那些已定向的成肌细胞分化为有功能的、可收缩的肌肉。两个转录因子家族在这些过程中起关键作用。生肌碱性螺旋 - 环 - 螺旋（bHLH）蛋白，MyoD和Myf5，是成肌细胞特化所必需的，而同一家族的两个成员，肌细胞生成素和MRF4，在体内成肌细胞分化中起关键作用。生肌bHLH家族的所有四个成员在被引入培养的多种非肌细胞时，都足以显性诱导肌生成，然而这种功能需要第二个转录调节因子家族，即肌细胞增强因子2（MEF - 2）家族的活性。MEF2因子对肌肉分化至关重要，先前的研究表明MyoD和MEF2家族成员协同作用以激活转录和肌生成。与这些观察结果一致，大多数骨骼肌基因需要MyoD和MEF2家族成员来激活其转录。这种激活的组合模型可能存在一个例外，即观察到生肌bHLH因子可能能够独立激活MEF2的表达。这就提出了一个问题，即MyoD因子如何在没有MEF2协同激活的情况下诱导mef2基因转录。在骨骼肌发育过程中，mef2c是MEF2家族中第一个表达的成员。在这项研究中，我们使用转基因方法研究了小鼠mef2c基因中一个骨骼肌特异性增强子的调控。我们表明，在体内mef2c是MyoD家族通过mef2c骨骼肌增强子中的一个关键E盒的直接转录靶标，并且我们表明mef2c不是MEF2自动调节的直接靶标。（C）2003爱思唯尔爱尔兰有限公司。保留所有权利。
Skeletal muscle development requires the coordinated expression of numerous transcription factors to control the specification of mesodermal progenitor cells to a muscle fate and the differentiation of those committed myoblasts into functional, contractile muscle. Two families of transcription factors play key roles in these processes. The myogenic basic helix-loop-helix (bHLH) proteins, MyoD and Myf5, are required for myoblast specification, while two members of the same family, myogenin and MRF4, play key roles in myoblast differentiation in vivo. All four members of the myogenic bHLH family are sufficient to dominantly induce myogenesis when introduced into a variety of non-muscle cells in culture, however this function requires the activity of a second fan-lily of transcriptional regulators, the myocyte enhancer factor 2 (MEF-2) family. MEF2 factors are essential for muscle differentiation, and previous studies have shown that MyoD and MEF2 family members function combinatorially to activate transcription and myogenesis. Consistent with these observations, the majority of skeletal muscle genes require both MyoD and MEF2 family members to activate their transcription. A possible exception to this combinatorial model for activation is suggested by the observation that myogenic bHLH factors may be able to independently activate the expression of MEF2. This raises the question as to how mef2 gene transcription is induced by MyoD factors without cooperative activation by MEF2. During skeletal muscle development, mef2c is the first member of the MEF2 family to be expressed. In this study, we have investigated the regulation of a skeletal muscle-specific enhancer from the mouse mef2c gene using a transgenic approach. We show that mef2c is a direct transcriptional target of the MyoD family in vivo via an essential E box in the skeletal muscle enhancer of mef2c, and we show that mef2c is not a direct target for autoregulation by MEF2. (C) 2003 Elsevier Ireland Ltd. All rights reserved.