Identification of the transactivation domain of the transcription factor Sox-2 and an associated co-activator

The importance of interactions between Sox and POU transcription factors in the regulation of gene expression is becoming increasingly apparent. Recen tly, many examples of the involvement of Sox-POU partnerships in transcript ion have been discovered, including a partnership between Sox-2 and Oct-3, Little is known about the mechanisms by which these factors modulate transc ription. To better understand the molecular interactions involved, we mappe d the location of the transactivation domain of Sox-2. This was done in the context of its interaction with Oct-3, as well as its ability to trans act ivate as a fusion protein linked to the DNA-binding domain of Gal4. Both ap proaches demonstrated that Sox-2 contains a transactivation domain in its C -terminal half, containing a serine-rich region and the C-terminus. We also determined that the viral oncoprotein Ela inhibits the ability of the Ga14 /Sox-2 fusion protein to transactivate, as well as the transcriptional acti vation mediated by the combined action of Sox-a and Oct-3, In contrast, a m utant form of E1a, unable to bind p300, lacks both of these effects. Import antly, we determined that p300 overcomes the inhibitory effects of Ela in b oth assays. Together, these findings suggest that Sox-2 mediates its effect s, at least in part, through the co-activator p300.