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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.

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.