Nature Genetics
34, 199 - 202 (2003)
Published online: 11 May 2003; | doi:10.1038/ng1162
Trans allele methylation and paramutation-like effects in miceHerry Herman1, 2, 3, Michael Lu2, 4, Melly Anggraini2, Aimee Sikora2, Yanjie Chang2, Bong June Yoon2, 4
& Paul D Soloway1, 21
Cornell University, Division of Nutritional Sciences, Ithaca, New York, USA. 2
Roswell Park Cancer Institute, Buffalo, New York, USA. 3
Department of Orthopaedic Surgery, School of Medicine, Padjadjaran University-Hasan Sadikin General Hospital, Bandung, Indonesia. 4
Present addresses: National Cancer Institute, Bethesda, Maryland, USA (M.L.); Brown University, Department of Neuroscience, Providence, Rhode Island, USA (B.J.Y.).
Correspondence should be addressed to Paul D Soloway pds28@cornell.eduIn 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.
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