THE CHICKEN BETA EPSILON-GLOBIN ENHANCER DIRECTS AUTONOMOUSLY REGULATED, HIGH-LEVEL EXPRESSION OF THE CHICKEN EPSILON-GLOBIN GENE IN TRANSGENIC MICE/

In transiently transfected chicken erythroid cells, beta-like globin g ene switching is mediated through differential activation of the cis-l inked embryonic epsilon- and adult beta-globin genes by a shared enhan cer. Two underlying mechanisms have been proposed: (i) tissue- and sta ge-specific factors activate the beta-globin promoter in adult erythro id cells (autonomous regulation); and (ii) the epsilon-globin promoter , although transcriptionally competent in both embryonic and adult cel ls, is suppressed at the adult stage through competition with the beta -globin promoter for interaction with the enhancer (competitive regula tion). Analyses of transgenic mice carrying the chicken beta/epsilon-g lobin locus demonstrated that both genes depended on the enhancer for erythroid expression, but only the epsilon-globin gene exhibited devel opmentally appropriate transcription at levels comparable to the endog enous mouse globin genes. Surprisingly, the chicken epsilon-globin gen e also appeared to be autonomously regulated, as has been observed for human embryonic and fetal beta-like globin genes in transgenic mice. These results suggest that the chicken beta/epsilon-globin enhancer po ssesses either embryonic stage or epsilon-globin gene specificity when incorporated into the murine germ line.