The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis
The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis
复制标题
DOI：
10.1101/gad.12.3.422
复制
发表时间：
1998-02-01
影响因子：
10.5
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Cripps, RM;Black, BL;Olson, EN
MEF 2是果蝇肌肉发育所需的MADS盒转录因子。在这里，我们表明，bHLH转录因子Twist直接调节Mef 2在成人体肌前体细胞的表达，通过位于转录起始位点上游2245 bp的175 bp增强子。在该元件内，单个进化上保守的E盒对于增强子活性是必需的。Twist蛋白可以与该E盒结合以激活Mef 2转录，并且Twist的异位表达导致野生型175-bp增强子的异位激活。通过使用一个温度敏感的突变体的扭曲，我们表明，激活Mef 2转录通过这个增强子的扭曲是需要正常的成年肌肉发育，并减少扭曲功能的结果在表型类似于以前观察到的Mef 2突变成人。该175-bp增强子在胚胎中胚层中也有活性，表明该增强子在发育过程中多次发挥作用，并且其功能依赖于相同的保守E盒。在胚胎中，Twist功能的降低也强烈降低了Mef 2的表达。这些发现定义了骨骼肌发育所需的一种新的转录途径，并确定Twist是体细胞中胚层Mef 2表达的重要和直接调节因子。
MEF2 is a MADS-box transcription factor required for muscle development in Drosophila. Here, we show that the bHLH transcription factor Twist directly regulates Mef2 expression in adult somatic muscle precursor cells via a 175-bp enhancer located 2245 bp upstream of the transcriptional start site. Within this element, a single evolutionarily conserved E box is essential for enhancer activity. Twist protein can bind to this E box to activate Mef2 transcription, and ectopic expression of twist results in ectopic activation of the wild-type 175-bp enhancer. By use of a temperature-sensitive mutant of twist, we show that activation of Mef2 transcription via this enhancer by Twist is required for normal adult muscle development, and reduction in Twist function results in phenotypes similar to those observed previously in Mef2 mutant adults. The 175-bp enhancer is also active in the embryonic mesoderm, indicating that this enhancer functions at multiple times during development, and its function is dependent on the same conserved E box. In embryos, a reduction in Twist function also strongly reduced Mef2 expression. These findings define a novel transcriptional pathway required for skeletal muscle development and identify Twist as an essential and direct regulator of Mef2 expression in the somatic mesoderm.