The contribution of the human
globin gene promoters to tissue-specific transcription was studied by using
globin promoters to transcribe the neo (
G418 resistance) gene. After transfection into different cell types, neo gene expression was assayed by scoring colony formation in the presence of
G418. In K562 human
erythroleukemia cells, which express fetal and embryonic
globin genes but not the adult
beta-globin gene, the neo gene was expressed strongly from a fetal gamma- or embryonic
zeta-globin gene promoter but only weakly from the beta promoter. In murine
erythroleukemia cells which express the endogenous mouse beta genes, the neo gene was strongly expressed from both beta and gamma promoters. In two nonerythroid cell lines, human HeLa cells and mouse 3T3 fibroblasts, the
globin gene promoters did not allow neo gene expression.
Globin-neo genes were integrated in the
erythroleukemia cell genomes mostly as a single copy per cell and were transcribed from the appropriate
globin gene cap site. We conclude that
globin gene promoter sequences extending from -373 to +48 base pairs (bp) (relative to the cap site) for the beta gene, -385 to +34 bp for the gamma gene, and -555 to +38 bp for the zeta gene are sufficient for tissue-specific and perhaps developmentally specific transcription.