Regulation of alphaA-crystallin gene expression. Lens specificity achieved through the differential placement of similar transcriptional control elements in mouse and chicken.
The lens-preferred mouse alphaA-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 alphaA-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 alphaA-crystallin gene expression through AP-1-mediated regulatory mechanisms. We propose that the mouse and chicken alphaA-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.
Ilagan
J G
JG
Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2730, USA.
Cvekl
A
A
Kantorow
M
M
Piatigorsky
J
J
Sax
C M
CM
D000818:Animals; D002645:Chickens; D003459:Crystallins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D018808:Transcription Factor AP-1 / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D003459:Crystallins; D004268:DNA-Binding Proteins; D018808:Transcription Factor AP-1