AN E-BOX IN THE DESMIN PROMOTER COOPERATES WITH THE E BOX AND MEF-2 SITES OF A DISTAL ENHANCER TO DIRECT MUSCLE-SPECIFIC TRANSCRIPTION
AN E-BOX IN THE DESMIN PROMOTER COOPERATES WITH THE E BOX AND MEF-2 SITES OF A DISTAL ENHANCER TO DIRECT MUSCLE-SPECIFIC TRANSCRIPTION
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DOI：
10.1002/j.1460-2075.1994.tb06665.x
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发表时间：
1994-08-01
期刊：
影响因子：
11.4
通讯作者：
CAPETANAKI, Y
中科院分区：
文献类型：
--
作者：
LI, H;CAPETANAKI, Y
小鼠结蛋白基因的转录起始位点上游的前85个核苷酸含有E盒（E1），即螺旋-环-螺旋生肌调节剂的结合位点，足以赋予低水平的肌肉特异性表达。高水平的结蛋白表达是由于增强子，位于核苷酸-798和-976之间，其含有额外的E盒（E2）和肌肉特异性增强因子-2（MEF-2）结合位点。我们之前已经表明，myoD和肌细胞生成素都可以结合到近端（E1）和远端（E2）盒。在这里，我们证明，MEF-2C，肌细胞限制的成员MEF-2家族，可以结合结蛋白MEF-2网站。增强子活性的功能单元需要完整的E2和MEF-2元件。结蛋白增强子可以与E2盒或MEF-2位点相对良好地起作用，并且只有两者的突变消除转录增强;这两个元件的存在是最大增强子活性所需的。另一方面，突变的近端E1盒表明，这个元素是必不可少的结蛋白基因表达。E1与E2或MEF-2位点的双重突变表明，为了实现高水平的结蛋白基因表达，E1最有可能充当E2或MEF-2增强子元件发挥功能的中介。E1位点相对于TATA盒的位置是至关重要的。它的活性依赖于DNA的转角和距离。此外，该框似乎是10T1/2细胞中myoD和肌细胞生成素反式激活结蛋白的主要元件。它的失活减少了这些因子的反式激活;然而，MRF4和Myf5仍然可以部分发挥作用，可能是通过使用远端E2盒。
The first 85 nt upstream of the transcription initiation site of the mouse desmin gene, which contain an E box (El), the binding site of the helix - loop - helix myogenic regulators, are sufficient to confer low level muscle-specific expression, High levels of desmin expression are due to an enhancer, Located between nucleotides -798 and -976, which contains an additional E box (E2) and a muscle-specific enhancer factor-2 (MEF-2) binding site. We have previously shown that both myoD and myogenin can bind to the proximal (E1) and distal (E2) boxes. Here we demonstrate that MEF-2C, a myocyte-restricted member of the MEF-2 family, can bind to the desmin MEF-2 site. Functional units for the enhancer activity required intact E2 and MEF-2 elements. The desmin enhancer can function relatively well with either the E2 box or the MEF-2 site and only mutation of both eliminates transcriptional enhancement; the presence of both of these elements is required for maximum enhancer activity. On the other hand, mutagenesis of just the proximal E1 box showed that this element is essential for desmin gene expression. Double mutations of El with E2 or MEF-2 sites suggested that, to achieve high levels of desmin gene expression, E1 serves most possibly as an intermediary for either E2 or MEF-2 enhancer elements to function, The location of the E1 site relative to the TATA box is crucial. Its activity is DNA turn- and distance-dependent. Furthermore, this box seems to be the main element for desmin transactivation by myoD and myogenin in 10T1/2 cells. Its inactivation diminishes the transactivation by these factors; MRF4 and Myf5, however, can still partially function, possibly by using the distal E2 box.