Functional cooperation of lens-specific and nonspecific elements in the delta 1-crystallin enhancer.

The expression of the chicken delta 1-crystallin gene is primarily regulated by the action of a lens-specific enhancer 1 kilobase long and located in the third intron of the gene (S. Hayashi, K. Goto, T. S. Okada, and H. Kondoh, Genes Dev. 1:818-828, 1987). The 120-base-long core segment is required for the activity of the delta 1-crystallin enhancer but by itself shows no activity. We analyzed the action of the core and adjoining segments of the delta 1-crystallin enhancer by two different approaches: (i) multiplication of the segments to express any cryptic effect and (ii) competition among enhancers for nuclear factors involved in enhancer action. We found that (i) the core defines a strictly lens-specific element, (ii) an adjoining segment defines an element with a broad specificity with regard to cell type, (iii) these elements cooperate in cis within the delta 1-crystallin enhancer, (iv) the multimers of these elements complete with each other and with delta 1-crystallin and simian virus 40 enhancers in trans apparently without sequence specificity but in a fashion reflecting the strength of the enhancers, and (v) the enhancers in trans do not affect the expression of enhancer-free genes, thereby ruling out the possibility of competition for general transcription factors. The last two observations raise the possibility that the enhancer segments interacting with different sequence-specific factors also interact with one other component involved in enhancer action.