McDermott J C, Cardoso M C, Yu Y T, Andres V, Leifer D, Krainc D, Lipton S A, Nadal-Ginard B
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts.
Mol Cell Biol. 1993 Apr;13(4):2564-77. doi: 10.1128/mcb.13.4.2564-2577.1993.
The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783-1798, 1992). Here, we report the isolation and functional characterization of cDNA clones encoding four MEF2 factors derived from a separate gene that we have named hMEF2C. In contrast to those of the previously reported genes, the transcripts of the hMEF2C gene are restricted to skeletal muscle and brain. One of the alternate exons is exclusively present in brain transcripts. The products of this gene have DNA-binding and trans-activating activities indistinguishable from those of the previously reported MEF2 factors. The hMEF2C gene is induced late during myogenic differentiation, and its expression is limited to a subset of cortical neurons. The potential targets for this transcription factor in a subset of neurons are not known at this time. The strict tissue-specific pattern of expression of hMEF2C in comparison with the more ubiquitous expression of other MEF2 genes suggests a different mode of regulation and a potentially important role of hMEF2C factors in myogenesis and neurogenesis.
肌细胞增强子结合因子2(MEF2)位点是许多肌肉特异性增强子和启动子的关键元件,可与肌肉和大脑中的核蛋白结合。最近,我们克隆了一个由两个基因产生的MEF2转录因子家族,在mRNA水平上,它们广泛表达,并通过转录后过程产生组织特异性异构体(Y.-T. Yu、R. E. Breitbart、L. B. Smoot、Y. Lee、V. Mahdavi和B. Nadal-Ginard,《基因与发育》6:1783 - 1798,1992年)。在此,我们报告了编码来自一个单独基因的四种MEF2因子的cDNA克隆的分离和功能特性,我们将该基因命名为hMEF2C。与先前报道的基因不同,hMEF2C基因的转录本仅限于骨骼肌和大脑。其中一个可变外显子仅存在于大脑转录本中。该基因的产物具有与先前报道的MEF2因子无法区分的DNA结合和反式激活活性。hMEF2C基因在成肌分化后期被诱导,其表达仅限于皮质神经元的一个子集。目前尚不清楚该转录因子在一部分神经元中的潜在靶标。与其他MEF2基因更广泛的表达相比,hMEF2C严格的组织特异性表达模式表明其调控方式不同,并且hMEF2C因子在肌生成和神经发生中可能具有重要作用。