Muscle cell differentiation is inhibited by the helix-loop-helix protein Id3.
Muscle cell differentiation is inhibited by the helix-loop-helix protein Id3.
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发表时间：
1996-08
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通讯作者：
I. Melnikova;Barbara A. Christy
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作者：
I. Melnikova;Barbara A. Christy
Id 3（最初命名为HLH 462）属于螺旋-环-螺旋转录因子Id家族。Id家族的成员不包含邻近螺旋-环-螺旋二聚化结构域的碱性DNA结合区，因此，假设其通过防止功能性二聚体的形成而充当其他螺旋-环-螺旋蛋白的负调节剂。我们研究了Id 3在控制肌细胞分化中的潜在作用。Id 3 mRNA在增殖的成肌细胞中以高水平表达，并在诱导分化后下调。我们表明，稳定的过度表达的Id 3 mRNA抑制分化的溶胶8肌细胞系。Id 3的HLH和COOH末端结构域对于其在肌细胞中的显性负活性是必要和充分的。与野生型或载体转染的细胞相比，从Id 3过表达细胞制备的核提取物中存在的DNA结合活性显著降低。最后，我们通过原位杂交表明，Id 3 mRNA与肌生成调节因子肌生成素在体节和胚胎发育过程中的肌肉中共表达，尽管与肌生成调节因子不同，Id 3也在胚胎的许多其他位置表达。这些数据支持一种模型，其中Id 3通过抑制生肌调节因子的DNA结合活性来负调节肌肉分化。
Id3 (originally named HLH462) belongs to the Id family of the helix-loop-helix transcription factors. Members of the Id family do not contain basic DNA binding regions adjacent to the helix-loop-helix dimerization domain and are, therefore, hypothesized to act as negative regulators of other helix-loop-helix proteins by preventing the formation of functional dimers. We have investigated the potential role of Id3 in the control of muscle cell differentiation. Id3 mRNA is expressed at a high level in proliferating myoblasts and is down-regulated following induction of differentiation. We show that stable overexpression of Id3 mRNA inhibits differentiation of the Sol 8 muscle cell line. Both the HLH and COOH-terminal domains of Id3 are necessary and sufficient for its dominant-negative activity in muscle cells. DNA-binding activity present in nuclear extracts prepared from Id3-overexpressing cells was significantly reduced when compared to the wild-type or vector-transfected cells. Finally, we show by in situ hybridization that the Id3 mRNA is co-expressed with the myogenic regulatory factor myogenin in somites and developing muscle during embryogenesis, although unlike the myogenic regulatory factors, Id3 is also expressed in many other locations in the embryo. These data support a model in which Id3 negatively regulates muscle differentiation by inhibiting the DNA-binding activities of the myogenic regulatory factors.