Friedl E M, Matthias P
Friedrich Miescher-Institut, P. O. Box 2543, CH-4002 Basel, Switzerland.
J Biol Chem. 1996 Jun 14;271(24):13927-30. doi: 10.1074/jbc.271.24.13927.
The lymphoid-specific transcription factor Oct-2a is implicated in B cell-specific transcriptional activity via the octamer motif. Structure/function analysis of various Oct-2a effector regions in the context of the GAL4 DNA-binding domain revealed that Oct-2a contains two functionally different activation domains at the N and the C termini. The transcriptional activity of both domains is strongly potentiated by interactions with distinct B cell-specific coactivators. Recently, we have identified a repression domain located within the N terminus of Oct-2a (amino acids 2-99). When this domain was transferred to a potent activator, transcription was strongly inhibited. In this study we present a deletion analysis of the N-terminal region of Oct-2a to determine the minimal repression domain. We identified a stretch of 23 amino acids, rich in serine and threonine residues, which was responsible for most of the repression activity. We show that repression is strongly dependent on the type of enhancer present in the reporter plasmid as well as on the cell line tested. The possibility that Oct-2a can act as an activator and/or a repressor may have important consequences for the function of Oct-2a in B cell differentiation and other developmental processes.
淋巴特异性转录因子Oct-2a通过八聚体基序参与B细胞特异性转录活性。在GAL4 DNA结合结构域背景下对各种Oct-2a效应区域进行的结构/功能分析表明,Oct-2a在N端和C端包含两个功能不同的激活结构域。这两个结构域的转录活性通过与不同的B细胞特异性共激活因子相互作用而得到强烈增强。最近,我们在Oct-2a的N端(氨基酸2 - 99)鉴定出一个抑制结构域。当该结构域转移到一个强效激活因子上时,转录受到强烈抑制。在本研究中,我们对Oct-2a的N端区域进行缺失分析以确定最小抑制结构域。我们鉴定出一段由23个富含丝氨酸和苏氨酸残基的氨基酸组成的序列,它负责大部分的抑制活性。我们表明,抑制强烈依赖于报告质粒中存在的增强子类型以及所测试的细胞系。Oct-2a能够作为激活因子和/或抑制因子发挥作用,这一可能性可能对Oct-2a在B细胞分化和其他发育过程中的功能具有重要影响。