Testis-specific expression of a metallothionein I-driven transgene correlates with undermethylation of the locus in testicular DNA

Kourosh Salehi-Ashtiani, R. J. Widrow, C. L. Markert, E. Goldberg

    Research output: Contribution to journalArticle

    Abstract

    Mice carrying a chimeric transgene of the human testis-specific lactate dehydrogenase cDNA driven by mouse metallothionein I promoter have been reported to express the transgene in a testis-specific manner in six founder lines. To study the mechanism by which this testis-specific expression is mediated, we have examined genomic placement, expression pattern, and methylation status of the transgene. Our results indicate that transgene expression is repressed in all somatic tissues examined even when heavy metals are administered. Nuclear run-on assays indicate that failure of expression in the liver (in which the metallothionein I promoter is highly active) occurs at the transcriptional level. In contrast, the transgene mRNA is transcribed in male germ cells and is developmentally regulated during spermatogenesis. Examination of the transgene methylation status reveals that expression is inversely correlated with hypermethylation of the locus; all CpG dinucleotides examined in the promoter region were found to be fully methylated in kidney and liver but were undermethylated in testis. Since methylation of the murine metallothionein I promoter is sufficient to inhibit its activity, it is likely that suppression of the transgene in somatic tissues is mediated by methylation.

    Original languageEnglish (US)
    Pages (from-to)8886-8890
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume90
    Issue number19
    DOIs
    StatePublished - Oct 29 1993

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    Metallothionein
    Transgenes
    Testis
    DNA
    Methylation
    Liver
    Spermatogenesis
    Heavy Metals
    L-Lactate Dehydrogenase
    Genetic Promoter Regions
    Germ Cells
    Complementary DNA
    Kidney
    Messenger RNA

    ASJC Scopus subject areas

    • Genetics
    • General

    Cite this

    Testis-specific expression of a metallothionein I-driven transgene correlates with undermethylation of the locus in testicular DNA. / Salehi-Ashtiani, Kourosh; Widrow, R. J.; Markert, C. L.; Goldberg, E.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 19, 29.10.1993, p. 8886-8890.

    Research output: Contribution to journalArticle

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    AU - Salehi-Ashtiani, Kourosh

    AU - Widrow, R. J.

    AU - Markert, C. L.

    AU - Goldberg, E.

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