Martin J F, Schwarz J J, Olson E N
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5282-6. doi: 10.1073/pnas.90.11.5282.
MEF-2 is a muscle-specific DNA binding activity that recognizes an A+T-rich sequence found in the control regions of numerous muscle-specific genes. The recent cloning of MEF-2 showed that it belongs to the MADS (MCM1, Agamous, Deficiens, and serum-response factor) box family of transcription factors and that MEF-2 mRNA is expressed ubiquitously. Here we describe the cloning of a member of the MEF-2 gene family, referred to as MEF-2C, that is nearly identical to other MEF-2 gene products in the MADS box but diverges from other members of the family outside of this domain. MEF-2C binds the MEF-2 site with high affinity and can activate transcription of a reporter gene linked to tandem copies of that site. In contrast to previously described members of the MEF-2 family, MEF-2C transcripts are highly enriched in skeletal muscle, spleen, and brain of adult mice and are upregulated during myoblast differentiation. These results suggest that the MEF-2 site is a target for a diverse family of proteins that regulates transcription in a variety of cell types.
MEF-2是一种肌肉特异性DNA结合活性物质,可识别众多肌肉特异性基因调控区域中富含A+T的序列。最近对MEF-2的克隆表明,它属于转录因子的MADS(MCM1、无配子生殖、缺陷型和血清反应因子)盒家族,且MEF-2 mRNA在全身广泛表达。在此,我们描述了MEF-2基因家族一个成员的克隆,该成员被称为MEF-2C,它在MADS盒中与其他MEF-2基因产物几乎相同,但在该结构域之外与家族其他成员不同。MEF-2C以高亲和力结合MEF-2位点,并能激活与该位点串联拷贝相连的报告基因的转录。与先前描述的MEF-2家族成员不同,MEF-2C转录本在成年小鼠的骨骼肌、脾脏和大脑中高度富集,并在成肌细胞分化过程中上调。这些结果表明,MEF-2位点是一个多样化蛋白质家族的靶点,这些蛋白质在多种细胞类型中调节转录。