Regulation of alpha A-crystallin gene expression - Lens specificity achieved through the differential placement of similar transcriptional control elements in mouse and chicken

The lens-preferred mouse alpha A-crystallin gene contains a conserved stret ch (proximal element 2, +24/+43) in its 5'-noncoding region that we have pr eviously shown binds nuclear proteins of lens and non-lens cells. The 5'-ha lf of this sequence (PE2A, +25/+32) has consensus binding sites for AP-1 an d other transcription factors. We show here by deletion experiments that PE 2A is important for activity of the mouse alpha A-crystallin promoter and m ediates phorbol ester and c-Jun responsiveness of this promoter in transfec ted lens cells. In vitro protein binding studies suggest that AP-1 complexe s are capable of binding to PE2A. Our findings suggest that PE2A plays a ro le in mouse alpha A-crystallin gene expression through AP-1-mediated regula tory mechanisms. We propose that the mouse and chicken alpha A-crystallin g enes are expressed with lens specificity using a similar assortment of tran scription factors but with a different physical arrangement of their respec tive cis-elements within the promoter region. A fundamental role for AP-1 i n lens-preferred expression of crystallin genes is consistent with the idea that a redox-sensitive mechanism is a selective force for recruiting lens crystallins.