Transactivation by CIITA, the type II bare lymphocyte syndrome-associated factor, requires participation of multiple regions of the TATA box binding protein.

CIITA is a positive regulator of class II major histocompatibility complex gene transcription that has been found to be defective in one of the five complementation groups of class II major histocompatibility complex-negative cell lines. Its N-terminal region is capable of activating transcription from a reporter gene when fused to a DNA binding domain. We have investigated the mechanism of transactivation mediated by the CIITA activation domain by studying its role in the process of transcription initiation and elongation. Specifically the altered specificity TBP (TATA box binding protein) assay has been used to analyze the response of the CIITA activation domain to mutations in TBP known to disrupt its interaction with its associated general factors. Transactivation by CIITA was extremely sensitive to a mutation in TBP that in yeast is known to abolish VP16-mediated transcription but leaves basal transcription unaffected. A TBP mutant defective in interaction with TBP-associated factor TAFII250 also failed to mediate transactivation through the CIITA activation domain. Certain interactions between TBP and general factors that are specifically required for acidic activation domains were also required for CIITA-mediated transactivation to reach its full potential. Finally, like VP16, CIITA was able to stimulate elongation of transcription. Overall the mechanism of transactivation by the human B-cell-specific CIITA is very similar to that mediated by the herpes virus transactivator VP16 in the ways that have been tested.