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 stretch (proximal element 2, +24/+43) in its 5'-noncoding region that we have previously shown binds nuclear proteins of lens and non-lens cells. The 5'-half of this sequence (PE2A, +25/+32) has consensus binding sites for AP-1 and other transcription factors. We show here by deletion experiments that PE2A is important for activity of the mouse alpha A- crystallin promoter and mediates phorbol ester and c-Jun responsiveness of this promoter in transfected lens cells. In vitro protein binding studies suggest that AP-1 complexes are capable of binding to PE2A. Our findings suggest that PE2A plays a role in mouse alpha A-crystallin gene expression through AP-1-mediated regulatory mechanisms. We propose that the mouse and chicken alpha A-crystallin genes are expressed with lens specificity using a similar assortment of transcription factors but with a different physical arrangement of their respective cis-elements within the promoter region. A fundamental role for AP-1 in lens-preferred expression of crystallin genes is consistent with the idea that a redox-sensitive mechanism is a selective force for recruiting lens crystallins.