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Activation of humanα 1,-antitrypsin genes in rat hepatoma × human fibroblast hybrid cell lines is correlated with demethylation

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Somatic Cell and Molecular Genetics

Abstract

Alpha-1-antitrypsin (AAT) is the major protease inhibitor in human serum and is primarily expressed in the liver. We have studied AAT expression infusion hybrids between a rat hepatoma line and either human fetal liver fibroblasts (series XXII) or human skin fibroblasts (series XIX). While the human AAT gene was always activated in series XXII hybrids when it was present, it was only rarely activated in series XIX hybrids. RFLP analysis revealed that both parental AAT alleles in series XIX hybrids were capable of being activated. Molecular analysis of the AAT gene in expressing and nonexpressing hybrids revealed that active AAT genes were hypomethylated, while inactive AAT genes were highly methylated. However, differences in methylation patterns were confined to the 5′ end of the gene, on both sides of the first exon. DNasel sensitivity revealed no hypersensitive sites close to active or inactive AAT genes.

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Authors and Affiliations

  1. Department of Human Genetics, Yale University School of Medicine, 06510, New Haven, Connecticut

    David E. Barton & Uta Francke

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  1. David E. Barton
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  2. Uta Francke
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Barton, D.E., Francke, U. Activation of humanα 1,-antitrypsin genes in rat hepatoma × human fibroblast hybrid cell lines is correlated with demethylation. Somat Cell Mol Genet 13, 635–644 (1987). https://doi.org/10.1007/BF01534484

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  • DOI: https://doi.org/10.1007/BF01534484

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