Regulated expression of human globin genes and flanking DNA in mouse erythroleukemia--human cell hybrids.

The expression of human globin genes and intergenic DNA is being investigated in MEL-human hybrids containing intact human chromosomes derived from nonerythroid cells. The studies indicate that a factor(s) present in MEL cells can cause activation of both beta- and gamma-globin genes that can be further stimulated by treatment with DMSO, an inducer of MEL cell differentiation. MEL-lymphoblast and MEL-fibroblast hybrids express an adult-like program in which much larger amounts of beta-globin mRNA than gamma-globin mRNA are produced; human beta-globin is at least as efficient as mouse beta-globin gene expression. The expression of both beta- and gamma-globin genes appears to be normal, as their mRNAs were found in polyribosomes and human beta-globin chains were readily detected. These results suggest that the MEL cells may be exploited as recipients of human globin genes for studies of molecular mechanisms controlling their expression. Comparison of intergenic DNA transcription patterns in hybrids and other cells not expressing human beta-globin has led to the identification of two regions flanking the delta-beta-globin locus whose transcription is correlated with beta-globin. One region 3' to the beta gene may define the site where its transcription terminates. Transcription of the other region, which is 5' to the delta gene, may be involved in some unknown way in hemoglobin switching.