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Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.

Suzuki S, Ono R, Narita T, Pask AJ, Shaw G, Wang C, Kohda T, Alsop AE, Marshall Graves JA, Kohara Y, Ishino F, Renfree MB, Kaneko-Ishino T - PLoS Genet. (2007)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT
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.

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Allelic Expression Analysis of Tammar PEG10 and Neighboring GenesThe individual animal numbers are shown above the graphs and the pictures. The pairs of white and grey bars in the graphs represent the two parental alleles in each individual. The vertical axes represent the expression ratios of each allele percentage of total expression, and the raw data are shown under each bar. The characters under the raw data indicate the residues at each polymorphic site, and asterisks are added to the paternal alleles in the informative cases. The gel picture for No. 5 shows the result of RT-PCR for the individual with a PEG10 length polymorphism. Parental origin of both alleles are represented by “P” for paternal and “M” for maternal, respectively. The picture for No. 9 shows the results of direct sequencing for each PCR product. The arrows indicate the polymorphic sites.
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pgen-0030055-g002: Allelic Expression Analysis of Tammar PEG10 and Neighboring GenesThe individual animal numbers are shown above the graphs and the pictures. The pairs of white and grey bars in the graphs represent the two parental alleles in each individual. The vertical axes represent the expression ratios of each allele percentage of total expression, and the raw data are shown under each bar. The characters under the raw data indicate the residues at each polymorphic site, and asterisks are added to the paternal alleles in the informative cases. The gel picture for No. 5 shows the result of RT-PCR for the individual with a PEG10 length polymorphism. Parental origin of both alleles are represented by “P” for paternal and “M” for maternal, respectively. The picture for No. 9 shows the results of direct sequencing for each PCR product. The arrows indicate the polymorphic sites.

Mentions: In mice, there is a large imprinting cluster near Peg10 which includes the paternally expressed Sgce gene [22,23] Ppp1r9a, which is maternally biased in extraembryonic tissues [23] and Asb4, which is completely maternally expressed in both embryos and the extraembryonic tissues [23,24]. Tammar PEG10 showed almost complete monoallelic expression in all individuals. Paternal expression was confirmed in two embryos and one yolk sac placenta sample (Figure 2). Unexpectedly, tammar SGCE showed predominantly biallelic expression with only a small paternal bias, despite a short 200-bp distance between the transcription start sites of PEG10 and SGCE (Figure 2). PPP1R9A and ASB4 showed biallelic expression without parental bias (Figure 2). These results clearly demonstrate that imprinting in this region is restricted to the PEG10 gene in the tammar. As described above, the eutherian PEG10 imprinted region includes several neighboring genes, suggesting that the imprinted region expanded in the eutherians while in marsupials imprinting was restricted to PEG10.


Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.

Suzuki S, Ono R, Narita T, Pask AJ, Shaw G, Wang C, Kohda T, Alsop AE, Marshall Graves JA, Kohara Y, Ishino F, Renfree MB, Kaneko-Ishino T - PLoS Genet. (2007)

Allelic Expression Analysis of Tammar PEG10 and Neighboring GenesThe individual animal numbers are shown above the graphs and the pictures. The pairs of white and grey bars in the graphs represent the two parental alleles in each individual. The vertical axes represent the expression ratios of each allele percentage of total expression, and the raw data are shown under each bar. The characters under the raw data indicate the residues at each polymorphic site, and asterisks are added to the paternal alleles in the informative cases. The gel picture for No. 5 shows the result of RT-PCR for the individual with a PEG10 length polymorphism. Parental origin of both alleles are represented by “P” for paternal and “M” for maternal, respectively. The picture for No. 9 shows the results of direct sequencing for each PCR product. The arrows indicate the polymorphic sites.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851980&req=5

pgen-0030055-g002: Allelic Expression Analysis of Tammar PEG10 and Neighboring GenesThe individual animal numbers are shown above the graphs and the pictures. The pairs of white and grey bars in the graphs represent the two parental alleles in each individual. The vertical axes represent the expression ratios of each allele percentage of total expression, and the raw data are shown under each bar. The characters under the raw data indicate the residues at each polymorphic site, and asterisks are added to the paternal alleles in the informative cases. The gel picture for No. 5 shows the result of RT-PCR for the individual with a PEG10 length polymorphism. Parental origin of both alleles are represented by “P” for paternal and “M” for maternal, respectively. The picture for No. 9 shows the results of direct sequencing for each PCR product. The arrows indicate the polymorphic sites.
Mentions: In mice, there is a large imprinting cluster near Peg10 which includes the paternally expressed Sgce gene [22,23] Ppp1r9a, which is maternally biased in extraembryonic tissues [23] and Asb4, which is completely maternally expressed in both embryos and the extraembryonic tissues [23,24]. Tammar PEG10 showed almost complete monoallelic expression in all individuals. Paternal expression was confirmed in two embryos and one yolk sac placenta sample (Figure 2). Unexpectedly, tammar SGCE showed predominantly biallelic expression with only a small paternal bias, despite a short 200-bp distance between the transcription start sites of PEG10 and SGCE (Figure 2). PPP1R9A and ASB4 showed biallelic expression without parental bias (Figure 2). These results clearly demonstrate that imprinting in this region is restricted to the PEG10 gene in the tammar. As described above, the eutherian PEG10 imprinted region includes several neighboring genes, suggesting that the imprinted region expanded in the eutherians while in marsupials imprinting was restricted to PEG10.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus