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

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

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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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