ACTIVATION OF THE ALPHA-INTERNEXIN PROMOTER BY THE BRN-3A TRANSCRIPTION FACTOR IS DEPENDENT ON THE N-TERMINAL REGION OF THE PROTEIN

The Brn-3a, Brn-3b, and Brn-3c proteins are closely related POU (Pit-O ct-Unc) family transcription factors which are expressed predominantly in neuronal cells, We have identified the alpha-internexin gene as th e first reported, neuronally expressed, target gene whose promoter act ivity is modulated by these factors, Both the Brn-3a and Brn-3c factor s can activate the alpha-internexin promoter while Brn-3b represses it and can prevent activation by Brn-3a. Using chimeric constructs conta ining different regions of Brn-3a or Brn-3b, we show that activation o f the alpha-internexin promoter requires the N-terminal region of Brn- 3a. In contrast the activation by Brn-3a but not Brn-3b, of an artific ial promoter containing a synthetic Brn-3 binding site can be shown us ing the same constructs to be dependent on the POU domain of Brn-3a. M oreover, the isolated POU domain of Brn-3a can activate this artificia l promoter but not the alpha-internexin promoter. Hence Brn-3a contain s two distinct transactivation domains, at the N terminus and within t he POU domain, whose effect is dependent upon the target promoter, The relationship of gene transactivation by Brn-3a to its ability to tran sform primary cells which is also dependent on the N-terminal region o f the protein is discussed.