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首页> 外文期刊>Molecular and Cellular Biology >An E box mediates activation and repression of the acetylcholine receptor delta-subunit gene during myogenesis.
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An E box mediates activation and repression of the acetylcholine receptor delta-subunit gene during myogenesis.

机译：E盒在成肌过程中介导乙酰胆碱受体δ-亚基基因的激活和抑制。

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The genes encoding the skeletal muscle acetylcholine receptor (AChR) are induced during muscle development and are regulated subsequently by innervation. Because both the initiation and the subsequent regulation of AChR expression are controlled by transcriptional mechanisms, an understanding of the steps that regulate AChR expression following innervation is likely to require knowledge of the pathway that activates AChR genes during myogenesis. Thus, we sought to identify the cis-acting sequences that regulate expression of the AChR delta-subunit gene during muscle differentiation. We transfected muscle and nonmuscle cell lines with gene fusions between 5'-flanking DNA from the AChR delta-subunit gene and the human growth hormone gene, and we show here that 148 bp of 5'-flanking DNA from the AChR delta-subunit gene contains two regulatory elements that control muscle-specific gene expression. One element is an E box, which is important both for activation of the delta-subunit gene in myotubes and for its repression in myoblasts and nonmuscle cells. Mutation of this E box, which prevents binding of MyoD-E2A and myogenin-E2A heterodimers, decreases expression in myotubes and increases expression in myoblasts and nonmuscle cells. An E-box binding activity, which does not contain MyoD, myogenin, or E2A proteins, is present in muscle and nonmuscle cells and may be responsible for repressing the delta-subunit gene in myoblasts and nonmuscle cells. An enhancer, which lacks E boxes, is also required for expression of the delta-subunit gene but does not confer muscle-specific expression.
机译：编码骨骼肌乙酰胆碱受体（AChR）的基因在肌肉发育过程中被诱导，并随后受神经支配。由于AChR表达的启动和后续调节均受转录机制控制，因此对神经支配后调节AChR表达的步骤的理解可能需要了解在成肌过程中激活AChR基因的途径。因此，我们试图确定在肌肉分化过程中调节AChRδ亚基基因表达的顺式作用序列。我们用来自AChR delta亚基基因的5'侧翼DNA与人类生长激素基因之间的基因融合体转染了肌肉和非肌肉细胞系，在这里我们显示了来自AChR delta亚基基因的5'侧翼DNA 148 bp包含两个控制元件，可控制肌肉特异性基因的表达。一个元件是E盒，E盒对于激活肌管中的δ-亚基基因及其在成肌细胞和非肌细胞中的抑制都很重要。该E框的突变阻止了MyoD-E2A和肌生成素-E2A异二聚体的结合，从而降低了肌管中的表达并增加了成肌细胞和非肌细胞中的表达。 E-box结合活性不包含MyoD，肌生成素或E2A蛋白，存在于肌肉和非肌肉细胞中，可能负责抑制成肌细胞和非肌肉细胞中的delta亚基基因。缺失E框的增强子对于表达δ亚基基因也是必需的，但是不赋予肌肉特异性表达。

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