| Abstract: | Employing δ-crystallin gene as a model, we have investigated tissue-specific gene regulation. Our approach was to analyze regulatory elements associated with the gene utilizing gene transfer techniques. Introduction of the chicken δ1-crystallin gene into the genome of developing mouse embryos resulted in lens-specific expression, indicating that the elements governing the tissue specificity are located in the DNA sequence introduced. Through analysis of various regions of the δ1-crystallin gene and the associated DNA sequences, we identified a lens-specific enhancer in the third intron of the gene. It was demonstrated that this enhancer alone is sufficient to account for lens specificity of the δ1-crystallin gene. Dissection of the δ1-crystallin enhancer and functional assessment by multiplication of enhancer fragments demonstrated the cooperative interaction of lens-specific and nonspecific elements in the enhancer. The mechanism by which heterologous elements cooperate in generating enhancer activity unquestionably provides great flexibility to the regulatory system, and may account for developmental modulation of gene activity superimposed on tissue specificity. |
