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The chicken beta/epsilon-globin enhancer directs autonomously regulated, high-level expression of the chicken epsilon-globin gene in transgenic mice.

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  • 1. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208.
      Authors
    • Foley KP 1
    (1 author)

Proceedings of the National Academy of Sciences of the United States of America, 01 Jul 1994, 91(15):7252-7256
https://doi.org/10.1073/pnas.91.15.7252 PMID: 8041775 PMCID: PMC44377

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Abstract 

In transiently transfected chicken erythroid cells, beta-like globin gene switching is mediated through differential activation of the cis-linked embryonic epsilon- and adult beta-globin genes by a shared enhancer. Two underlying mechanisms have been proposed: (i) tissue- and stage-specific factors activate the beta-globin promoter in adult erythroid cells (autonomous regulation); and (ii) the epsilon-globin promoter, although transcriptionally competent in both embryonic and adult cells, is suppressed at the adult stage through competition with the beta-globin promoter for interaction with the enhancer (competitive regulation). Analyses of transgenic mice carrying the chicken beta/epsilon-globin locus demonstrated that both genes depended on the enhancer for erythroid expression, but only the epsilon-globin gene exhibited developmentally appropriate transcription at levels comparable to the endogenous mouse globin genes. Surprisingly, the chicken epsilon-globin gene 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 possesses either embryonic stage or epsilon-globin gene specificity when incorporated into the murine germ line.

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Proc Natl Acad Sci U S A. 1994 Jul 19; 91(15): 7252–7256.
PMCID: PMC44377
PMID: 8041775

The chicken beta/epsilon-globin enhancer directs autonomously regulated, high-level expression of the chicken epsilon-globin gene in transgenic mice.

K P Foley, S Pruzina, J D Winick, J D Engel, F Grosveld, and P Fraser
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Abstract

In transiently transfected chicken erythroid cells, beta-like globin gene switching is mediated through differential activation of the cis-linked embryonic epsilon- and adult beta-globin genes by a shared enhancer. Two underlying mechanisms have been proposed: (i) tissue- and stage-specific factors activate the beta-globin promoter in adult erythroid cells (autonomous regulation); and (ii) the epsilon-globin promoter, although transcriptionally competent in both embryonic and adult cells, is suppressed at the adult stage through competition with the beta-globin promoter for interaction with the enhancer (competitive regulation). Analyses of transgenic mice carrying the chicken beta/epsilon-globin locus demonstrated that both genes depended on the enhancer for erythroid expression, but only the epsilon-globin gene exhibited developmentally appropriate transcription at levels comparable to the endogenous mouse globin genes. Surprisingly, the chicken epsilon-globin gene 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 possesses either embryonic stage or epsilon-globin gene specificity when incorporated into the murine germ line.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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