Friedl E M, Matthias P
Friedrich Miescher-Institut, Basel, Switzerland.
Eur J Biochem. 1995 Nov 15;234(1):308-16. doi: 10.1111/j.1432-1033.1995.308_c.x.
The lymphoid-specific transcription factor Oct-2a contains two transcriptional activation domains which are located within the N-terminal and C-terminal regions. To study their differential activation properties, we linked the isolated effector domains to the GAL4 DNA-binding domain. We have shown that both activating regions of Oct-2a, isolated from their natural context, can activate transcription as promoter factors. In contrast to the C-terminus, activation by the N-terminal domain is dependent on a yet unidentified factor(s) binding to the simian virus 40 enhancer. The results obtained by duplication of activation domains or their mixed combination suggest that the domains are functionally independent. However, activation from a remote position could only be achieved with the C-terminus of Oct-2a in B cells. In lymphoid cells, higher activation levels were observed, suggesting that distinct B-cell-specific cofactors in concert with the effector domains of Oct-2a might be involved in mediating transcription from proximal and remote positions. Furthermore, we identified a repression domain at the N-terminus of Oct-2a. When transferred to a potent activator, transcriptional stimulation was inhibited efficiently. These results underscore the modular structure of Oct-2a with separable domains for activation and repression and suggest that Oct-2a might have complex regulatory functions in vivo.
淋巴特异性转录因子Oct-2a含有两个转录激活结构域,分别位于N端和C端区域。为了研究它们的差异激活特性,我们将分离出的效应结构域与GAL4 DNA结合结构域相连。我们已经表明,从其自然环境中分离出来的Oct-2a的两个激活区域都可以作为启动子因子激活转录。与C端不同,N端结构域的激活依赖于一种尚未确定的与猿猴病毒40增强子结合的因子。通过重复激活结构域或它们的混合组合获得的结果表明,这些结构域在功能上是独立的。然而,只有在B细胞中使用Oct-2a的C端才能从远距离位置实现激活。在淋巴细胞中观察到更高的激活水平,这表明与Oct-2a的效应结构域协同作用的不同B细胞特异性辅因子可能参与介导近端和远距离位置的转录。此外,我们在Oct-2a的N端鉴定出一个抑制结构域。当转移到一个有效的激活剂上时,转录刺激被有效地抑制。这些结果强调了Oct-2a具有可分离的激活和抑制结构域的模块化结构,并表明Oct-2a在体内可能具有复杂的调节功能。