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September 1, 1990Genes & DevelopmentOpen Access

A major positive regulatory region located far upstream of the human alpha-globin gene locus.

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Authors

DHDouglas R. HiggsUniversity College DublinWWW. G. WoodSutter HealthAJAndrew P. JarmanHoward Hughes Medical Institute

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Implication

Experimental study reveals a remote upstream enhancer driving high-level human alpha-globin expression in erythroid cells, suggesting coordinated regulation with beta-globin genes.

Key Points

  • To identify and characterize remote regulatory elements responsible for high-level, tissue-specific expression of the human alpha-globin gene cluster.
  • Linked the remote upstream DNA segment to the human alpha-globin gene and stably transfected mouse erythroleukemia cells to measure mRNA expression.
  • Generated transgenic mice containing the upstream region linked to the alpha-globin gene to evaluate erythroid tissue-specific mRNA and peripheral blood protein levels.
  • Mouse erythroleukemia transformants expressed human alpha-globin mRNA at levels equivalent to interspecific hybrids retaining intact human chromosome 16.
  • Transgenic mice exhibited robust, erythroid-specific human alpha-globin mRNA expression, with peripheral blood demonstrating detectable human alpha-globin protein chains.
  • The upstream region demonstrated position, structural, and functional parallels to the beta-globin dominant control region despite wider structural divergencies between the loci.

Cite This Study

Higgs et al. (1990) studied this question.

synapsesocial.com/papers/69dcca06c099bcfdbb133a5chttps://doi.org/10.1101/gad.4.9.1588
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