Black B L, Ligon K L, Zhang Y, Olson E N
Department of Molecular Biology and Oncology, Hamon Center for Basic Cancer Research, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
J Biol Chem. 1996 Oct 25;271(43):26659-63. doi: 10.1074/jbc.271.43.26659.
Establishment of skeletal muscle and neural cell types is controlled by families of myogenic and neurogenic basic helix-loop-helix (bHLH) proteins, respectively. Myogenic bHLH proteins have been shown to activate skeletal muscle transcription in collaboration with members of the myocyte enhancer factor-2 (MEF2) family of MCM1-agamous-deficiens-serum response factor (MADS)-box transcription factors, which are expressed in differentiated myocytes and neurons. Here, we show that the neurogenic bHLH protein MASH1 interacts with members of the MEF2 family and that this interaction, mediated by the DNA binding and dimerization domains of these factors, results in synergistic activation of transcription through either the MASH1 or the MEF2 DNA binding site. Consistent with their involvement in activation of neuronal gene expression, members of the MEF2 family are expressed in P19 embryonal carcinoma cells that have been induced to form neurons following treatment with retinoic acid. These results suggest that members of the MEF2 family perform similar roles in synergistic activation of transcription in myogenic and neurogenic lineages by serving as cofactors for cell type-specific bHLH proteins.
骨骼肌和神经细胞类型的建立分别受成肌和神经源性碱性螺旋-环-螺旋（bHLH）蛋白家族的控制。成肌bHLH蛋白已被证明可与肌细胞增强因子-2（MEF2）家族成员协同激活骨骼肌转录，MEF2家族属于MCM1-无配子-缺陷-血清反应因子（MADS）-盒转录因子家族，在分化的肌细胞和神经元中表达。在此，我们表明神经源性bHLH蛋白MASH1与MEF2家族成员相互作用，并且这种由这些因子的DNA结合和二聚化结构域介导的相互作用，通过MASH1或MEF2 DNA结合位点导致转录的协同激活。与它们参与神经元基因表达的激活一致，MEF2家族成员在经视黄酸处理后已被诱导形成神经元的P19胚胎癌细胞中表达。这些结果表明，MEF2家族成员通过作为细胞类型特异性bHLH蛋白的辅助因子，在成肌和神经源性谱系的转录协同激活中发挥类似作用。
