Trans allele methylation and paramutation-like effects in mice

Herry Herman, Michael Lu, Melly Anggraini, Aimee Sikora, Yanjie Chang, Bong June Yoon, Paul D. Soloway

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)


In mammals, imprinted genes have parent-of-origin-specific patterns of DNA methylation that cause allele-specific expression. At Rasgrf1 (encoding RAS protein-specific guanine nucleotide-releasing factor 1), a repeated DNA element is needed to establish methylation and expression of the active paternal allele1. At Igf2r (encoding insulin-like growth factor 2 receptor), a sequence called region 2 is needed for methylation of the active maternal allele2,3. Here we show that replacing the Rasgrf1 repeats on the paternal allele with region 2 allows both methylation and expression of the paternal copy of Rasgrf1, indicating that sequences that control methylation can function ectopically. Paternal transmission of the mutated allele also induced methylation and expression in trans of the normally unmethylated and silent wild-type maternal allele. Once activated, the wild-type maternal Rasgrf1 allele maintained its activated state in the next generation independently of the paternal allele. These results recapitulate in mice several features in common with paramutation described in plants4.

Original languageEnglish
Pages (from-to)199-202
Number of pages4
JournalNature Genetics
Issue number2
Publication statusPublished - 2003 Jun 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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