Trans allele methylation and paramutation-like effects in mice.
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 allele. At Igf2r (encoding insulin-like growth factor 2 receptor), a sequence called region 2 is needed for methylation of the active maternal allele. 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 plants.
Herman
Herry
H
Cornell University, Division of Nutritional Sciences, Ithaca, New York, USA.
Lu
Michael
M
Anggraini
Melly
M
Sikora
Aimee
A
Chang
Yanjie
Y
Yoon
Bong June
BJ
Soloway
Paul D
PD
D000483:Alleles; D000818:Animals; D003433:Crosses, Genetic; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D020690:GTPase-Activating Proteins; D020868:Gene Silencing; D018392:Genomic Imprinting; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins; D020666:ras-GRF1
C513041:Arhgap35 protein, mouse; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; C513037:Rasgrf1 protein, mouse; D012097:Repressor Proteins; D020666:ras-GRF1; D019204:GTP-Binding Proteins