THE OCT-1 POU-SPECIFIC DOMAIN CAN STIMULATE SMALL NUCLEAR-RNA GENE-TRANSCRIPTION BY STABILIZING THE BASAL TRANSCRIPTION COMPLEX SNAP(C)

The RNA polymerase II and III human small nuclear RNA promoters have a common basal element, the proximal sequence element, which binds the TATA box-binding protein-containing complex SNAP(c). They also contain an enhancer characterized by a highly conserved octamer sequence, whi ch constitutes a binding site for the broadly expressed POU domain tra nscription factor Oct-1, The POU domain is a bipartite DNA-binding dom ain consisting of a POU-homeo (POUH) domain and a POU-specific (POUS) domain joined by a flexible linker, Here, we show that the Oct-1 POU d omain but not the related Pit-1 POU domain can facilitate the binding of SNAP(c) to the proximal sequence element, and activate transcriptio n. The effect is probably mediated by protein-protein contacts, and 1 of 30 amino acid differences between the Oct-1 and Pit-1 POUS domains is the key determinant for the differential interaction with SNAP(c) a nd the ability to activate transcription, These results show that a fu nction that is the hallmark of activation domains, namely, recruitment of a basal transcription complex resulting in activation of transcrip tion, can be performed by a DNA-binding domain, In this case, subtle c hanges between activator DNA-binding domains, as subtle as a single am ino acid difference, can profoundly affect interaction with the basal transcription machinery.