Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.
Among mammals, only eutherians and marsupials are viviparous and have genomic imprinting that leads to parent-of-origin-specific differential gene expression. We used comparative analysis to investigate the origin of genomic imprinting in mammals. PEG10 (paternally expressed 10) is a retrotransposon-derived imprinted gene that has an essential role for the formation of the placenta of the mouse. Here, we show that an orthologue of PEG10 exists in another therian mammal, the marsupial tammar wallaby (Macropus eugenii), but not in a prototherian mammal, the egg-laying platypus (Ornithorhynchus anatinus), suggesting its close relationship to the origin of placentation in therian mammals. We have discovered a hitherto missing link of the imprinting mechanism between eutherians and marsupials because tammar PEG10 is the first example of a differentially methylated region (DMR) associated with genomic imprinting in marsupials. Surprisingly, the marsupial DMR was strictly limited to the 5' region of PEG10, unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the adjacent imprinted gene SGCE. These results not only demonstrate a common origin of the DMR-associated imprinting mechanism in therian mammals but provide the first demonstration that DMR-associated genomic imprinting in eutherians can originate from the repression of exogenous DNA sequences and/or retrotransposons by DNA methylation.
Suzuki
Shunsuke
S
Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Ono
Ryuichi
R
Narita
Takanori
T
Pask
Andrew J
AJ
Shaw
Geoffrey
G
Wang
Changshan
C
Kohda
Takashi
T
Alsop
Amber E
AE
Marshall Graves
Jennifer A
JA
Kohara
Yuji
Y
Ishino
Fumitoshi
F
Renfree
Marilyn B
MB
Kaneko-Ishino
Tomoko
T
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian; D020868:Gene Silencing / Q000502:physiology*; D018392:Genomic Imprinting / Q000502:physiology*; D006801:Humans; D007614:Macropodidae / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D010987:Platypus / Q000235:genetics; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D018626:Retroelements / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C432965:PEG10 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D018626:Retroelements