ACTIVATION OF PHENOTYPIC-EXPRESSION OF HUMAN GLOBIN GENES FROM NON-ERYTHROID CELLS BY CHROMOSOME-DEPENDENT TRANSFER TO TETRAPLOID MOUSE ERYTHROLEUKEMIA-CELLS

Chromosome-dependent gene transfer mediated by cell function was used to show that it is possible to activate phenotypic expression of human α globin genes derived from nonerythroid cells. Hybrid cells containing the human α globin structural genes were derived by fusion of populations of adult human peripheral blood mononuclear cells (devoid of identifiable erythroid cells) with adenine phosphoribosyl-transferase-deficient mouse erythroleukemia cells that contained close to a tetraploid complement of mouse chromosomes. The hybrid cells retained a near tetraploid complement of mouse chromosomes but had lost 80% of the chromosomes of the human parent cell. All of these hybrid cells and their subclones, which contained human chromosome 16, exhibited synthesis of human α globin chains. Human α globin mRNA was also demonstrated to be present in one of these hybrid cells by RNA.cDNA molecular hybridization analysis. We conclude that the mechanism responsible for restricting expression of the human globin genes in nonerythroid cells is not irreversible, at least for those globin structural genes that are actively transcribed in erythroid cells during adult life. Moreover, some genetic factor or process in the tetraploid mouse erythroleukemia cell is, under the conditions of our experiments, capable of reactivating phenotypic expression (production of globin chains) of human globin genes derived from nonerythroid hematopoietic cells after chromosome-dependent gene transfer.