Selective suppression of endogenous beta-globin gene expression by transferred beta-globin/TK chimeric gene in murine...

To examine the effect of gene transfer on expression of the endogenous beta-globin gene in murine erythroleukemia (MEL) cells, a beta-globin/TK chimeric gene was introduced into MEL cells. In some of the transformants, expression of the endogenous beta-globin gene was only weakly induced with the addition of DMSO, while expression of the introduced beta-globin/TK chimeric gene was well induced. Suppression of the endogenous beta-globin gene is selective for beta-globin gene, since expression of alpha-globin gene was only weakly affected in its induction in the transformants. Analysis of nine individual transformants indicated that suppression of the endogenous gene correlates more closely with the transcriptional activity than the copy number of the exogenous gene. Thus, the selective suppression can be explained by competition of positive trans-acting factor(s), present in limiting amounts, with high copy number of the exogenous gene the conformation of which is active.