AN INTRON-1 REGULATORY REGION FROM THE MURINE ADENOSINE-DEAMINASE GENE CAN ACTIVATE HETEROLOGOUS PROMOTERS FOR UBIQUITOUS EXPRESSION IN TRANSGENIC MICE

Ubiquitously expressed genes contain regulatory features which allow e xpression in virtually all cell types. In an effort to understand the molecular basis for this regulatolyfeature, the chromatin structure of the murine adenosine deaminase gene was examined by DNase I digestion in nuclei of several tissues. The promoter contained a strong hyperse nsitive site in all tissues examined, including those with very high a nd very low levels of ADA expression. Transgenic mouse studies reveale d that a 3.3 kb EcoRI (3.3EE) fragment from intron I was required to g enerate a strong promoter DNase I hypersensitive site, and to produce ubiquitous expression. The 3.3EE fragment also contained a thymic enha ncer activity which mapped to sequences conserved with the human ADA g ene T-lymphocyte enhancer Mutational analysis indicated that ubiquitou s expression was not dependent on the presence of a functional thymic enhancer Both the thymic enhancer and the ubiquitous activator within the 3.3EE fragment functioned with heterologous promoters in transgeni c mice.