OCA-B is a functional analog of VP16 but targets a separate surface of the Oct-1 POU domain

OCA-B is a B-cell-specific coregulator of the broadly expressed POU domain transcription factor Oct-1, OCA-B associates with the Oct-1 POU domain, a bipartite DNA-binding structure containing a POU-specific (POUS) domain joined by a flexible linker to a POU homeodomain (POUH), Here, we show that OCA-B alters the activity of Oct-1 in two ways, It provides a transcriptional activation domain which, unlike Oct-1, activates an mRNA-type promoter effectively, and it stabilizes Oct-1 on the Oct-1-responsive octamer sequence ATGCAAAT, These properties of OCA-B parallel those displayed by the herpes simplex virus Oct-1 coregulator VP16, OCA-B, however, interacts with a different surface of the DNA-bound Oct-1 POU domain, interacting with both the POUS and POUH domains and the center of the ATGCAAAT octamer sequence. The OCA-B and VP16 interactions with the Oct-1 POU domain are sufficiently different to permit OCA-B and VP16 to bind the Oct-1 POU domain simultaneously, These results emphasize the structural versatility of the Oct-1 POU domain in its interaction with coregulators.