THE MYOD DNA-BINDING DOMAIN CONTAINS A RECOGNITION CODE FOR MUSCLE-SPECIFIC GENE ACTIVATION
THE MYOD DNA-BINDING DOMAIN CONTAINS A RECOGNITION CODE FOR MUSCLE-SPECIFIC GENE ACTIVATION
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DOI：
10.1016/0092-8674(90)90088-v
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发表时间：
1990-03-09
期刊：
影响因子：
64.5
通讯作者：
WEINTRAUB, H
中科院分区：
文献类型：
--
作者：
DAVIS, RL;CHENG, PF;WEINTRAUB, H
肌原性决定基因MyoD的60个氨基酸结构域对于体外序列特异性DNA结合和转染的C3 H10 T1/2细胞的肌原性转化是必要的和足够的。我们发现，一个高度碱性的区域，直接上游的螺旋-环-螺旋（HLH）寡聚化基序，需要MyoD DNA体外结合。用果蝇T4无毛鳞片蛋白（外周神经发生所需）的类似序列取代螺旋1、螺旋2或MyoD环对体外DNA结合或转染的C3 H10 T1/2细胞中肌肉特异性基因激活没有实质性影响。然而，用其他HLH蛋白的类似序列（免疫球蛋白增强子结合E12蛋白或T4无鞭毛蛋白）替换MyoD的碱性区域允许体外DNA结合，但消除了肌肉特异性基因激活。这些发现表明，确定肌肉特异性基因激活的识别代码位于MyoD碱性区域内，并且特异性DNA结合的能力不足以激活肌肉程序。
A 60 amino acid domain of the myogenic determination gene MyoD is necessary and sufficient for sequence-specific DNA binding in vitro and myogenic conversion of transfected C3H10T1/2 cells. We show that a highly basic region, immediately upstream of the helix-loop-helix (HLH) oligomerization motif, is required for MyoD DNA binding in vitro. Replacing helix1, helix2, or the loop of MyoD with the analogous sequence of the Drosophila T4 achaete-scute protein (required for peripheral neurogenesis) has no substantial effect on DNA binding in vitro or muscle-specific gene activation in transfected C3H10T1/2 cells. However, replacing the basic region of MyoD with the analogous sequence of other HLH proteins (the immunoglobulin enhancer binding E12 protein or T4 achaetescute protein) allows DNA binding in vitro, yet abolishes muscle-specific gene activation. These findings suggest that a recognition code that determines muscle-specific gene activation lies within the MyoD basic region and that the capacity for specific DNA binding is insufficient to activate the muscle program.