FOS AND JUN REPRESS TRANSCRIPTIONAL ACTIVATION BY MYOGENIN AND MYOD - THE AMINO TERMINUS OF JUN CAN MEDIATE REPRESSION
FOS AND JUN REPRESS TRANSCRIPTIONAL ACTIVATION BY MYOGENIN AND MYOD - THE AMINO TERMINUS OF JUN CAN MEDIATE REPRESSION
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DOI：
10.1101/gad.6.4.676
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发表时间：
1992-04-01
影响因子：
10.5
通讯作者：
OLSON, EN
中科院分区：
文献类型：
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作者：
LI, L;CHAMBARD, JC;OLSON, EN
肌细胞生成素和MyoD属于肌肉特异性螺旋-环-螺旋（HLH）蛋白家族，其具有激活非肌细胞中肌肉特异性基因的潜力。肽生长因子可以阻断肌细胞生成素和MyoD激活其靶基因的能力。在这里，我们表明，生长因子诱导的原癌基因c-fos，c-jun和junB模拟外源性生长因子的影响，并抑制肌生成素和MyoD的反式激活的肌肉肌酸激酶（MCK）增强子。相反，JunD与JunB和c-Jun共享DNA结合特异性，但在肌细胞中组成型表达，是肌细胞生成素和MyoD反式激活能力的无效抑制剂。Fos和Jun的转录抑制是肌源性HLH蛋白特异性的，并且在广泛表达的HLH蛋白E47中没有观察到，其识别相同的DNA序列。Fos和Jun对MCK增强子的抑制作用靶向于肌细胞生成素和MyoD DNA识别序列，并可由c-Jun的氨基末端介导。这些结果表明，Jun家族的成员可以根据其对肌肉特异性转录的影响来区分，并表明控制肌生成的转录因子与参与细胞增殖的转录因子之间存在串扰。
Myogenin and MyoD belong to a family of muscle-specific helix-loop-helix (HLH) proteins that have the potential to activate muscle-specific genes in nonmyogenic cells. Peptide growth factors can block the ability of myogenin and MyoD to activate their target genes. Here, we show that the growth factor-inducible proto-oncogenes c-fos, c-jun, and junB mimic the effects of exogenous growth factors and suppress trans-activation of the muscle creatine kinase (MCK) enhancer by myogenin and MyoD. In contrast, JunD, which shares DNA-binding specificity with JunB and c-Jun but is expressed constitutively in muscle cells, is an inefficient inhibitor of the trans-activating capacity of myogenin and MyoD. Transcriptional repression by Fos and Jun is specific to myogenic HLH proteins and is not observed with the widely expressed HLH protein E47, which recognizes the same DNA sequence. Repression of the MCK enhancer by Fos and Jun is targeted at the myogenin and MyoD DNA recognition sequence and can be mediated by the amino terminus of c-Jun. Comparison of several myogenin mutants for their responsiveness to Fos and Jun shows that repression is directed at the basic-HLH region. These results indicate that members of the Jun family can be distinguished on the basis of their effects on muscle-specific transcription and suggest there is cross talk between transcription factors that control myogenesis and those involved in cell proliferation.