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Upstream G gamma-globin and downstream beta-globin sequences required for stage-specific expression in transgenic mice.

M Trudel·J Magram·L Bruckner·F Costantini
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Abstract

The human G gamma-globin and beta-globin genes are expressed in erythroid cells at different stages of human development, and previous studies have shown that the two cloned genes are also expressed in a differential stage-specific manner in transgenic mice. The G gamma-globin gene is expressed only in murine embryonic erythroid cells, while the beta-globin gene is active only at the fetal and adult stages. In this study, we analyzed transgenic mice carrying a series of hybrid genes in which different upstream, intragenic, or downstream sequences were contributed by the beta-globin or G gamma-globin gene. We found that hybrid 5'G gamma/3'beta globin genes containing G gamma-globin sequences upstream from the initiation codon were expressed in embryonic erythroid cells at levels similar to those of an intact G gamma-globin transgene. In contrast, beta-globin upstream sequences were insufficient for expression of 5'beta/3'G gamma hybrid globin genes or a beta-globin-metallothionein fusion gene in adult erythroid cells. However, beta-globin downstream sequences, including 212 base pairs of exon III and 1,900 base pairs of 3'-flanking DNA, were able to activate a 5'G gamma/3'beta hybrid globin gene in fetal and adult erythroid cells. These experiments suggest that positive regulatory elements upstream from the G gamma-globin and downstream from the beta-globin gene are involved in the differential expression of the two genes during development.

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AnimalsDNA Restriction EnzymesGene Expression RegulationGenesGlobinsHumansMetallothioneinMiceMice, TransgenicRNA, MessengerTranscription, GeneticJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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M Trudel, J Magram, L Bruckner, F Costantini. 1987. Upstream G gamma-globin and downstream beta-globin sequences required for stage-specific expression in transgenic mice.. https://doi.org/10.1128/mcb.7.11.4024-4029.1987

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