Thatikunta P, Qin W, Christy B A, Tennekoon G I, Rutkowski J L
Children's Hospital of Philadelphia and the Department of Neurology, University of Pennsylvania, 19104-4318, USA.
Mol Cell Neurosci. 1999 Dec;14(6):519-28. doi: 10.1006/mcne.1999.0799.
Id proteins are thought to act as dominant negative antagonists of basic helix-loop-helix (bHLH) transcription factors that direct differentiation in various cell types. We found that Schwann cells express all four Id-family genes and that their transcript levels were reciprocally regulated in pairs during nerve maturation in vivo and cAMP-mediated differentiation in vitro. The rapid induction as part of the early response to axonal membranes and cytokines suggested that Id3 is involved in myelin gene repression. An inverse relationship between Id1/3 and myelin P0 expression was consistent with a role for these two Id proteins as inhibitors of differentiation, and Id1/3 proteins strongly repressed myelin gene promoter activity. Nuclear factors isolated from Schwann cells and intact sciatic nerves were found to bind three different HLH recognition sequences (E boxes) in the proximal region of the P0 promoter, and production of these DNA binding complexes was altered during differentiation. These data support the concept that Id proteins regulate myelin gene expression by controlling the formation of specific bHLH DNA binding complexes with different E-box preferences.
Id蛋白被认为是碱性螺旋-环-螺旋（bHLH）转录因子的显性负性拮抗剂，这些转录因子指导各种细胞类型的分化。我们发现雪旺细胞表达所有四个Id家族基因，并且在体内神经成熟和体外cAMP介导的分化过程中，它们的转录水平成对地相互调节。作为对轴突膜和细胞因子早期反应的一部分，Id3的快速诱导表明它参与了髓鞘基因的抑制。Id1/3与髓鞘P0表达之间的负相关关系与这两种Id蛋白作为分化抑制剂的作用一致，并且Id1/3蛋白强烈抑制髓鞘基因启动子活性。从雪旺细胞和完整坐骨神经中分离出的核因子被发现可结合P0启动子近端区域的三种不同的HLH识别序列（E盒），并且这些DNA结合复合物的产生在分化过程中发生了改变。这些数据支持了这样的概念，即Id蛋白通过控制具有不同E盒偏好的特定bHLH DNA结合复合物的形成来调节髓鞘基因表达。
