Despite their descent from a common ancestral gene and the requirement for coordinated, tissue-specific regulation, the - and -globin genes in many mammals are regulated in distinctly different ways. Unlike the -globin gene, the rabbit -globin gene is transiently expressed at a high level without an added enhancer in transfected erythroid and non-erythroid cells. By examining a series of / fusion genes, we show that internal sequences of the rabbit -globin gene (within the first two exons and introns) are required along with the 5` flank for this enhancer-independent expression. Furthermore, deletion of the introns of the -globin gene, or replacement by introns of the -globin gene, results in severely decreased expression of the transfecting genes. Hybrid constructs between segments of the -globin gene and a luciferase gene confirm that internal -globin sequences are needed for high level production of RNA in transfected cells. The flanking and internal sequences implicated in regulation of the rabbit -globin gene coincide with a prominent CpG-rich island and may comprise an extended promoter (including both flanking and intragenic sequences) that is active in transfected cells without an enhancer.

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