The human CD34 antigen is expressed specifically on human hematopoietic stem cells and not on mature blood cells, and CD34+ cells can reconstitute normal hematopoiesis of all cell lineages. CD34 is still the best defined human stem cell marker and is therefore a model for stem cell gene expression. Previous studies have defined some of the promoter elements for human and murine CD34, but the regulation of this and other stem cell genes is still very poorly understood, The distal elements necessary for human CD34 expression in vivo were recently isolated. The goal of this project is to continue to define and analyze the control elements of CD34, and to characterize those elements of the CD34 gene which can direct stem ceil expression of heterologous genes. The characterization of these elements could lead to the development of new vectors for gene therapy, as well as new understanding of the factors regulating genes in stem cells. Therefore, the specific aims are to characterize and study the regulatory elements of CD34 in the following steps: 1. To further characterize the important control elements regulating human CD34 gene expression in stem cells. 2. To characterize DNA binding proteins which regulate these elements. 3. To use CD34 regulatory elements expressing Cre recombinase and the tetracycline transactivator to enable tissue specific, regulatable expression of heterologous genes in the stem cell compartment.
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