Gene expression in somatic cell hybrids derived from embryonic mice transgenic for human globin genes

Somatic cell hybrids have been used previously to investigate the developmental regulation of globin gene expression. When a chromosome containing an active human fetal gamma gene is transferred to mouse erythroleukaemia (MEL) cells by cell fusion, there is persistent expression of this gene through multiple hybrid-cell divisions despite the 'adult' trans-acting factor environment of the MEL cell. We analysed hybrids formed between embryonic erythroblasts and MEL cells to determine whether the embryonic globin genes would be similarly regulated. Surprisingly, there was no detectable expression of either the endogenous (epsilon, beta h 1) or the transgenic (human epsilon) embryonic beta-like genes in a large number of hybrid pools and clones, even though these genes were expressed in the donor cells at the time of fusion. In contrast, the human gamma gene, which is also expressed as an embryonic gene in transgenic mice, continued to be expressed in these hybrids. This lack of embryonic gene expression in hybrids also applied to the alpha gene cluster; no mouse or human zeta mRNA was detectable in embryonic cell hybrids from mice transgenic for the human alphaglobin genes. Hybrids generated from embryonic non-erythroid cells resulted in expression that was largely restricted to the adult beta gene. It has previously been suggested that epigenetic modifications to the beta-globin gene cluster during normal development are responsible for the perpetuation of gamma and beta gene expression in this hybrid cell system. The results presented here suggest that no such stable modifications occur around the embryonic genes and therefore that the regulatory mechanisms determining embryonic globin gene transcription differ from those responsible for the expression of gamma and beta genes in this system.