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Takashi Kohda - One of the best experts on this subject based on the ideXlab platform.
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role of retrotransposon derived Imprinted Gene rtl1 in the feto maternal interface of mouse placenta
Nature Genetics, 2008Co-Authors: Yoichi Sekita, Takashi Kohda, Hirotaka Wagatsuma, Kenji Nakamura, Masayo Kagami, Noriko Wakisaka, Toshiaki Hino, Rika Suzukimigishima, Atsuo OguraAbstract:Role of retrotransposon-derived Imprinted Gene, Rtl1 , in the feto-maternal interface of mouse placenta
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retrotransposon silencing by dna methylation can drive mammalian genomic imprinting
PLOS Genetics, 2007Co-Authors: Shunsuke Suzuki, Takashi Kohda, Takanori Narita, Andrew J Pask, Geoffrey Shaw, Changshan Wang, Amber E Alsop, Jennifer Marshall A Graves, Yuji Kohara, Fumitoshi IshinoAbstract: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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deletion of peg10 an Imprinted Gene acquired from a retrotransposon causes early embryonic lethality
Nature Genetics, 2006Co-Authors: Kenji Nakamura, Toshiaki Hino, Rika Suzukimigishima, Kimiko Inoue, Mie Naruse, Takako Usami, Noriko Wakisakasaito, Narumi Ogonuki, Hiromi Miki, Takashi KohdaAbstract:By comparing mammalian genomes, we and others have identified actively transcribed Ty3/gypsy retrotransposon-derived Genes with highly conserved DNA sequences and insertion sites1,2,3,4,5,6. To elucidate the functions of evolutionarily conserved retrotransposon-derived Genes in mammalian development, we produced mice that lack one of these Genes, Peg10 (paternally expressed 10)1,2,3,7, which is a paternally expressed Imprinted Gene on mouse proximal chromosome 6. The Peg10 knockout mice showed early embryonic lethality owing to defects in the placenta. This indicates that Peg10 is critical for mouse parthenoGenetic development and provides the first direct evidence of an essential role of an evolutionarily conserved retrotransposon-derived Gene in mammalian development.
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identification of a large novel Imprinted Gene cluster on mouse proximal chromosome 6
Genome Research, 2003Co-Authors: Hirosuke Shiura, Takashi Kohda, Tomoko Kanekoishino, Hiroyuki Aburatani, Fumitoshi IshinoAbstract:Mice with maternal duplication of proximal chromosome 6 die in utero at an early embryonic stage. Recently, two Imprinted Genes, paternally expressed Sgce and maternally expressed Asb4, were identified in this region. This report analyzes the imprinting status of Genes within a 1-Mb region containing these two Genes. Peg10, which is next to Sgce, shows complete paternal expression, like Sgce. Conversely, Neurabin, Pon2, and Pon3 show preferential maternal expression at embryonic stages, although they all show biallelic expression in neonatal tissues. These results demonstrate that there is a large novel Imprinted Gene cluster in this region. 5′-RACE (Rapid Amplification of cDNA Ends) analysis of Peg10 revealed the existence of a novel first exon separate from the second exon, which encoded two putative ORFs similar to the viral Gag and Pol proteins. A differentially methylated region established in sperm and eggs is located just within the region containing the two first exons of Peg10 and Sgce, and may play an important role in regulating the two paternally expressed Genes: Peg10 and Sgce.
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a retrotransposon derived Gene peg10 is a novel Imprinted Gene located on human chromosome 7q21
Genomics, 2001Co-Authors: Shin Kobayashi, Takashi Kohda, Kohzo Aisaka, Tomoko Kanekoishino, Hirotaka Wagatsuma, Fumitoshi IshinoAbstract:A novel paternally expressed Imprinted Gene, PEG10 (Paternally Expressed 10), was identified on human chromosome 7q21. PEG10 is located near the SGCE (Sarcoglycan e) Gene, whose mouse homologue was recently shown to be Imprinted. Therefore, it is highly possible that a new Imprinted Gene cluster exists on human chromosome 7q21. Analysis of two predicted open reading frames (ORF1 and ORF2) revealed that ORF1 and ORF2 have homology to the gag and pol proteins of some vertebrate retrotransposons, respectively. These data suggest that PEG10 is derived from a retrotransposon that was previously integrated into the mammalian genome. PEG10 is likely to be essential for understanding how exogenous Genes become Imprinted. © 2001 Academic Press
Tomoko Kanekoishino - One of the best experts on this subject based on the ideXlab platform.
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identification of a large novel Imprinted Gene cluster on mouse proximal chromosome 6
Genome Research, 2003Co-Authors: Hirosuke Shiura, Takashi Kohda, Tomoko Kanekoishino, Hiroyuki Aburatani, Fumitoshi IshinoAbstract:Mice with maternal duplication of proximal chromosome 6 die in utero at an early embryonic stage. Recently, two Imprinted Genes, paternally expressed Sgce and maternally expressed Asb4, were identified in this region. This report analyzes the imprinting status of Genes within a 1-Mb region containing these two Genes. Peg10, which is next to Sgce, shows complete paternal expression, like Sgce. Conversely, Neurabin, Pon2, and Pon3 show preferential maternal expression at embryonic stages, although they all show biallelic expression in neonatal tissues. These results demonstrate that there is a large novel Imprinted Gene cluster in this region. 5′-RACE (Rapid Amplification of cDNA Ends) analysis of Peg10 revealed the existence of a novel first exon separate from the second exon, which encoded two putative ORFs similar to the viral Gag and Pol proteins. A differentially methylated region established in sperm and eggs is located just within the region containing the two first exons of Peg10 and Sgce, and may play an important role in regulating the two paternally expressed Genes: Peg10 and Sgce.
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a retrotransposon derived Gene peg10 is a novel Imprinted Gene located on human chromosome 7q21
Genomics, 2001Co-Authors: Shin Kobayashi, Takashi Kohda, Kohzo Aisaka, Tomoko Kanekoishino, Hirotaka Wagatsuma, Fumitoshi IshinoAbstract:A novel paternally expressed Imprinted Gene, PEG10 (Paternally Expressed 10), was identified on human chromosome 7q21. PEG10 is located near the SGCE (Sarcoglycan e) Gene, whose mouse homologue was recently shown to be Imprinted. Therefore, it is highly possible that a new Imprinted Gene cluster exists on human chromosome 7q21. Analysis of two predicted open reading frames (ORF1 and ORF2) revealed that ORF1 and ORF2 have homology to the gag and pol proteins of some vertebrate retrotransposons, respectively. These data suggest that PEG10 is derived from a retrotransposon that was previously integrated into the mammalian genome. PEG10 is likely to be essential for understanding how exogenous Genes become Imprinted. © 2001 Academic Press
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identification of an Imprinted Gene meg3 gtl2 and its human homologue meg3 first mapped on mouse distal chromosome 12 and human chromosome 14q
Genes to Cells, 2000Co-Authors: Takashi Kohda, Naoki Miyoshi, Azim M Surani, Hirotaka Wagatsuma, Shigeharu Wakana, Toshihiko Shiroishi, Masashi Nomura, Kohzoh Aisaka, Tomoko KanekoishinoAbstract:Background The paternal duplication of mouse distal chromosome 12 leads to late embryonal/neonatal lethality and growth promotion, whereas maternal duplication leads to late embryonal lethality and growth retardation. Human paternal or maternal uniparental disomies of chromosome 14q that are syntenic to mouse distal chromosome 12 have also been reported to show some imprinting effects on growth, mental activity and musculoskeletal morphology. For the isolation of Imprinted Genes in this region, a systematic screen of maternally expressed Genes (Megs) was carried out by our subtraction-hybridization method using androGenetic and normally fertilized embryos. Results We have isolated seven candidate clones of the mouse Meg Gene. Among them, we identified a novel maternally expressed Imprinted Gene, Meg3, on mouse distal chromosome 12 and showed that it was identical to the Gtl2 Gene. We also found that the human homologue MEG3 on chromosome 14q was also monoallelically expressed. Conclusions This is the first identification of the imprinting Gene, both on mouse distal chromosome 12 and on human chromosome 14q, respectively. Because there are no obvious open reading frames in either the mouse Meg3/Gtl2 or human MEG3, the function of these Genes remains unclear. However, this result will provide a good basis for the further investigation of several important Imprinted Genes in this chromosomal region.
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identification of the meg1 grb10 Imprinted Gene on mouse proximal chromosome 11 a candidate for the silver russell syndrome Gene
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Naoki Miyoshi, Takashi Kohda, Yoshimi Kuroiwa, Azim M Surani, Hiroshi Shitara, Hiromichi Yonekawa, Tohru Kawabe, Hideaki Hasegawa, Sheilla C Barton, Tomoko KanekoishinoAbstract:In a systematic screen for maternally expressed Imprinted Genes using subtraction hybridization with androGenetic and normal fertilized mouse embryos, seven candidate maternally expressed Genes (Megs) have been isolated, including the H19 and p57Kip2 Genes that are known to be maternally expressed. Herein, we demonstrate that an Imprinted Gene, Meg1, is apparently identical to Grb10 (growth factor receptor-bound protein 10), which is located on mouse proximal chromosome 11. Grb10 protein was reported to bind to the insulin receptor and/or the insulin-like growth factor (IGF) I receptor via its src homology 2 domain and to inhibit the associated tyrosine kinase activity that is involved in the growth promoting activities of insulin and IGFs (IGF-I and -II). Thus, it is probable that Meg1/Grb10 is responsible for the Imprinted effects of prenatal growth retardation or growth promotion caused by maternal or paternal duplication of proximal chromosome 11 with reciprocal deficiencies (MatDp.prox11 or PatDp.prox11), respectively. In the human, it has been reported that the maternal uniparental disomy 7 is responsible for the Silver–Russell syndrome (SRS) whose effects include pre- and postnatal growth retardation and other dysmorphologies. The human homologue GRB10 on chromosome 7q11.2–12 is a candidate Gene for Silver–Russell syndrome.
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human peg1 mest an Imprinted Gene on chromosome 7
Human Molecular Genetics, 1997Co-Authors: Shin Kobayashi, Takashi Kohda, Naoki Miyoshi, Yoshimi Kuroiwa, Kohzo Aisaka, Osamu Tsutsumi, Tomoko Kanekoishino, Fumitoshi IshinoAbstract:: The mouse Peg1/Mest Gene is an Imprinted Gene that is expressed particularly in mesodermal tissues in early embryonic stages. It was the most abundant Imprinted Gene among eight paternally expressed Genes (Peg 1-8) isolated by a subtraction-hybridization method from a mouse embryonal cDNA library. It has been mapped to proximal mouse chromosome 6, maternal duplication of which causes early embryonic lethality. The human chromosomal region that shares syntenic homology with this is 7q21-qter, and human maternal uniparental disomy 7 (UPD 7) causes apparent growth deficiency and slight morphological abnormalities. Therefore, at least one paternally expressed Imprinted Gene seems to be present in this region. In this report, we demonstrate that human PEG1/MEST is an Imprinted Gene expressed from a paternal allele and located on chromosome 7q31-34, near D7S649. It is the first Imprinted Gene mapped to human chromosome 7 and a candidate for a Gene responsible for primordial growth retardation including Silver-Russell syndrome (SRS).
Naoki Miyoshi - One of the best experts on this subject based on the ideXlab platform.
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mouse peg9 dlk1 and human peg9 dlk1 are paternally expressed Imprinted Genes closely located to the maternally expressed Imprinted Genes mouse meg3 gtl2 and human meg3
Genes to Cells, 2000Co-Authors: Shin Kobayashi, Takashi Kohda, Naoki Miyoshi, Kohzo Aisaka, Hirotaka Wagatsuma, Atsuo Ogura, Hitoshi Ichikawa, Masaaki Yamazaki, Hiroyuki Tashiro, Misao OhkiAbstract:BACKGROUND: Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of Imprinted Genes has been extensively carried out to identify the Genes responsible for Imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed Imprinted Genes (Pegs). We compared the resulting expression profiles of parthenoGenetic and fertilized control embryos to identify novel Imprinted Genes. RESULTS: A novel paternally expressed mouse Imprinted Gene, Peg9/Dlk1, was identified. Consistent with this finding, the paternal expression of its human homologue, PEG9/DLK1, was also confirmed. These two Genes form Imprinted Gene clusters with the reciprocally Imprinted mouse Meg3/Gtl2 and human MEG3 Genes that we first identified on distal chromosome 12 and chromosome 14q32, respectively. CONCLUSIONS: As DNA chip technology allows us to quickly screen a large number of Genes, using this technology to search for Imprinted Genes could accelerate the identification of Genes responsible for human and mouse Genetic diseases. Dlk1 and DLK1, which encode transmembrane proteins, have six EGF-like repeats and show homology to the Delta Gene in Drosophila melanogaster. Because of its homology to mammalian Delta homologues, PEG9/DLK1 may contribute to the scoliosis phenotype observed in maternal uniparental disomy 14 (mUPD14) patients.
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Mouse Peg9/Dlk1 and human PEG9/DLK1 are paternally expressed Imprinted Genes closely located to the maternally expressed Imprinted Genes: mouse Meg3/Gtl2 and human MEG3.
Genes to Cells, 2000Co-Authors: Shin Kobayashi, Takashi Kohda, Naoki Miyoshi, Kohzo Aisaka, Hirotaka Wagatsuma, Hitoshi Ichikawa, Masaaki Yamazaki, Hiroyuki Tashiro, Atsuo OguraAbstract:BACKGROUND: Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of Imprinted Genes has been extensively carried out to identify the Genes responsible for Imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed Imprinted Genes (Pegs). We compared the resulting expression profiles of parthenoGenetic and fertilized control embryos to identify novel Imprinted Genes. RESULTS: A novel paternally expressed mouse Imprinted Gene, Peg9/Dlk1, was identified. Consistent with this finding, the paternal expression of its human homologue, PEG9/DLK1, was also confirmed. These two Genes form Imprinted Gene clusters with the reciprocally Imprinted mouse Meg3/Gtl2 and human MEG3 Genes that we first identified on distal chromosome 12 and chromosome 14q32, respectively. CONCLUSIONS: As DNA chip technology allows us to quickly screen a large number of Genes, using this technology to search for Imprinted Genes could accelerate the identification of Genes responsible for human and mouse Genetic diseases. Dlk1 and DLK1, which encode transmembrane proteins, have six EGF-like repeats and show homology to the Delta Gene in Drosophila melanogaster. Because of its homology to mammalian Delta homologues, PEG9/DLK1 may contribute to the scoliosis phenotype observed in maternal uniparental disomy 14 (mUPD14) patients.
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identification of an Imprinted Gene meg3 gtl2 and its human homologue meg3 first mapped on mouse distal chromosome 12 and human chromosome 14q
Genes to Cells, 2000Co-Authors: Takashi Kohda, Naoki Miyoshi, Azim M Surani, Hirotaka Wagatsuma, Shigeharu Wakana, Toshihiko Shiroishi, Masashi Nomura, Kohzoh Aisaka, Tomoko KanekoishinoAbstract:Background The paternal duplication of mouse distal chromosome 12 leads to late embryonal/neonatal lethality and growth promotion, whereas maternal duplication leads to late embryonal lethality and growth retardation. Human paternal or maternal uniparental disomies of chromosome 14q that are syntenic to mouse distal chromosome 12 have also been reported to show some imprinting effects on growth, mental activity and musculoskeletal morphology. For the isolation of Imprinted Genes in this region, a systematic screen of maternally expressed Genes (Megs) was carried out by our subtraction-hybridization method using androGenetic and normally fertilized embryos. Results We have isolated seven candidate clones of the mouse Meg Gene. Among them, we identified a novel maternally expressed Imprinted Gene, Meg3, on mouse distal chromosome 12 and showed that it was identical to the Gtl2 Gene. We also found that the human homologue MEG3 on chromosome 14q was also monoallelically expressed. Conclusions This is the first identification of the imprinting Gene, both on mouse distal chromosome 12 and on human chromosome 14q, respectively. Because there are no obvious open reading frames in either the mouse Meg3/Gtl2 or human MEG3, the function of these Genes remains unclear. However, this result will provide a good basis for the further investigation of several important Imprinted Genes in this chromosomal region.
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identification of the meg1 grb10 Imprinted Gene on mouse proximal chromosome 11 a candidate for the silver russell syndrome Gene
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Naoki Miyoshi, Takashi Kohda, Yoshimi Kuroiwa, Azim M Surani, Hiroshi Shitara, Hiromichi Yonekawa, Tohru Kawabe, Hideaki Hasegawa, Sheilla C Barton, Tomoko KanekoishinoAbstract:In a systematic screen for maternally expressed Imprinted Genes using subtraction hybridization with androGenetic and normal fertilized mouse embryos, seven candidate maternally expressed Genes (Megs) have been isolated, including the H19 and p57Kip2 Genes that are known to be maternally expressed. Herein, we demonstrate that an Imprinted Gene, Meg1, is apparently identical to Grb10 (growth factor receptor-bound protein 10), which is located on mouse proximal chromosome 11. Grb10 protein was reported to bind to the insulin receptor and/or the insulin-like growth factor (IGF) I receptor via its src homology 2 domain and to inhibit the associated tyrosine kinase activity that is involved in the growth promoting activities of insulin and IGFs (IGF-I and -II). Thus, it is probable that Meg1/Grb10 is responsible for the Imprinted effects of prenatal growth retardation or growth promotion caused by maternal or paternal duplication of proximal chromosome 11 with reciprocal deficiencies (MatDp.prox11 or PatDp.prox11), respectively. In the human, it has been reported that the maternal uniparental disomy 7 is responsible for the Silver–Russell syndrome (SRS) whose effects include pre- and postnatal growth retardation and other dysmorphologies. The human homologue GRB10 on chromosome 7q11.2–12 is a candidate Gene for Silver–Russell syndrome.
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Identification of the Meg1/Grb10 Imprinted Gene on mouse proximal chromosome 11, a candidate for the Silver–Russell syndrome Gene
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Naoki Miyoshi, Takashi Kohda, Yoshimi Kuroiwa, Hiroshi Shitara, Hiromichi Yonekawa, Tohru Kawabe, Hideaki Hasegawa, Sheilla C Barton, M. Azim Surani, Tomoko Kaneko-ishinoAbstract:In a systematic screen for maternally expressed Imprinted Genes using subtraction hybridization with androGenetic and normal fertilized mouse embryos, seven candidate maternally expressed Genes (Megs) have been isolated, including the H19 and p57Kip2 Genes that are known to be maternally expressed. Herein, we demonstrate that an Imprinted Gene, Meg1, is apparently identical to Grb10 (growth factor receptor-bound protein 10), which is located on mouse proximal chromosome 11. Grb10 protein was reported to bind to the insulin receptor and/or the insulin-like growth factor (IGF) I receptor via its src homology 2 domain and to inhibit the associated tyrosine kinase activity that is involved in the growth promoting activities of insulin and IGFs (IGF-I and -II). Thus, it is probable that Meg1/Grb10 is responsible for the Imprinted effects of prenatal growth retardation or growth promotion caused by maternal or paternal duplication of proximal chromosome 11 with reciprocal deficiencies (MatDp.prox11 or PatDp.prox11), respectively. In the human, it has been reported that the maternal uniparental disomy 7 is responsible for the Silver–Russell syndrome (SRS) whose effects include pre- and postnatal growth retardation and other dysmorphologies. The human homologue GRB10 on chromosome 7q11.2–12 is a candidate Gene for Silver–Russell syndrome.
Fumitoshi Ishino - One of the best experts on this subject based on the ideXlab platform.
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Identification of an Imprinted Gene Cluster in the X-Inactivation Center
PLOS ONE, 2013Co-Authors: Shin Kobayashi, Yasushi Totoki, Miki Soma, Kazuya Matsumoto, Yoshitaka Fujihara, Atsushi Toyoda, Yoshiyuki Sakaki, Masaru Okabe, Fumitoshi IshinoAbstract:Mammalian development is strongly influenced by the epiGenetic phenomenon called genomic imprinting, in which either the paternal or the maternal allele of Imprinted Genes is expressed. Paternally expressed Xist, an Imprinted Gene, has been considered as a single cis-acting factor to inactivate the paternally inherited X chromosome (Xp) in preimplantation mouse embryos. This means that X-chromosome inactivation also entails Gene imprinting at a very early developmental stage. However, the precise mechanism of Imprinted X-chromosome inactivation remains unknown and there is little information about Imprinted Genes on X chromosomes. In this study, we examined whether there are other Imprinted Genes than Xist expressed from the inactive paternal X chromosome and expressed in female embryos at the preimplantation stage. We focused on small RNAs and compared their expression patterns between sexes by tagging the female X chromosome with green fluorescent protein. As a result, we identified two micro (mi)RNAs–miR-374-5p and miR-421-3p–mapped adjacent to Xist that were predominantly expressed in female blastocysts. Allelic expression analysis revealed that these miRNAs were indeed Imprinted and expressed from the Xp. Further analysis of the imprinting status of adjacent locus led to the discovery of a large cluster of Imprinted Genes expressed from the Xp: Jpx, Ftx and Zcchc13. To our knowledge, this is the first identified cluster of Imprinted Genes in the cis-acting regulatory region termed the X-inactivation center. This finding may help in understanding the molecular mechanisms regulating Imprinted X-chromosome inactivation during early mammalian development.
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retrotransposon silencing by dna methylation can drive mammalian genomic imprinting
PLOS Genetics, 2007Co-Authors: Shunsuke Suzuki, Takashi Kohda, Takanori Narita, Andrew J Pask, Geoffrey Shaw, Changshan Wang, Amber E Alsop, Jennifer Marshall A Graves, Yuji Kohara, Fumitoshi IshinoAbstract: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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identification of a large novel Imprinted Gene cluster on mouse proximal chromosome 6
Genome Research, 2003Co-Authors: Hirosuke Shiura, Takashi Kohda, Tomoko Kanekoishino, Hiroyuki Aburatani, Fumitoshi IshinoAbstract:Mice with maternal duplication of proximal chromosome 6 die in utero at an early embryonic stage. Recently, two Imprinted Genes, paternally expressed Sgce and maternally expressed Asb4, were identified in this region. This report analyzes the imprinting status of Genes within a 1-Mb region containing these two Genes. Peg10, which is next to Sgce, shows complete paternal expression, like Sgce. Conversely, Neurabin, Pon2, and Pon3 show preferential maternal expression at embryonic stages, although they all show biallelic expression in neonatal tissues. These results demonstrate that there is a large novel Imprinted Gene cluster in this region. 5′-RACE (Rapid Amplification of cDNA Ends) analysis of Peg10 revealed the existence of a novel first exon separate from the second exon, which encoded two putative ORFs similar to the viral Gag and Pol proteins. A differentially methylated region established in sperm and eggs is located just within the region containing the two first exons of Peg10 and Sgce, and may play an important role in regulating the two paternally expressed Genes: Peg10 and Sgce.
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a retrotransposon derived Gene peg10 is a novel Imprinted Gene located on human chromosome 7q21
Genomics, 2001Co-Authors: Shin Kobayashi, Takashi Kohda, Kohzo Aisaka, Tomoko Kanekoishino, Hirotaka Wagatsuma, Fumitoshi IshinoAbstract:A novel paternally expressed Imprinted Gene, PEG10 (Paternally Expressed 10), was identified on human chromosome 7q21. PEG10 is located near the SGCE (Sarcoglycan e) Gene, whose mouse homologue was recently shown to be Imprinted. Therefore, it is highly possible that a new Imprinted Gene cluster exists on human chromosome 7q21. Analysis of two predicted open reading frames (ORF1 and ORF2) revealed that ORF1 and ORF2 have homology to the gag and pol proteins of some vertebrate retrotransposons, respectively. These data suggest that PEG10 is derived from a retrotransposon that was previously integrated into the mammalian genome. PEG10 is likely to be essential for understanding how exogenous Genes become Imprinted. © 2001 Academic Press
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abnormal maternal behaviour and growth retardation associated with loss of the Imprinted Gene mest
Nature Genetics, 1998Co-Authors: Fumitoshi Ishino, Sheila C Barton, E B Keverne, Louis Lefebvre, Stephane Viville, Azim M SuraniAbstract:Mest (also known as Peg1), an Imprinted Gene expressed only from the paternal allele during development, was disrupted by Gene targeting in embryonic stem (ES) cells. The targeted mutation is Imprinted and reversibly silenced by passage through the female germ line. Paternal transmission activates the targeted allele and causes embryonic growth retardation associated with reduced postnatal survival rates in mutant progeny. More significantly, Mest-deficient females show abnormal maternal behaviour and impaired placentophagia, a distinctive mammalian behaviour. Our results provide evidence for the involvement of an Imprinted Gene in the control of adult behaviour.
Yoshimi Kuroiwa - One of the best experts on this subject based on the ideXlab platform.
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identification of the meg1 grb10 Imprinted Gene on mouse proximal chromosome 11 a candidate for the silver russell syndrome Gene
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Naoki Miyoshi, Takashi Kohda, Yoshimi Kuroiwa, Azim M Surani, Hiroshi Shitara, Hiromichi Yonekawa, Tohru Kawabe, Hideaki Hasegawa, Sheilla C Barton, Tomoko KanekoishinoAbstract:In a systematic screen for maternally expressed Imprinted Genes using subtraction hybridization with androGenetic and normal fertilized mouse embryos, seven candidate maternally expressed Genes (Megs) have been isolated, including the H19 and p57Kip2 Genes that are known to be maternally expressed. Herein, we demonstrate that an Imprinted Gene, Meg1, is apparently identical to Grb10 (growth factor receptor-bound protein 10), which is located on mouse proximal chromosome 11. Grb10 protein was reported to bind to the insulin receptor and/or the insulin-like growth factor (IGF) I receptor via its src homology 2 domain and to inhibit the associated tyrosine kinase activity that is involved in the growth promoting activities of insulin and IGFs (IGF-I and -II). Thus, it is probable that Meg1/Grb10 is responsible for the Imprinted effects of prenatal growth retardation or growth promotion caused by maternal or paternal duplication of proximal chromosome 11 with reciprocal deficiencies (MatDp.prox11 or PatDp.prox11), respectively. In the human, it has been reported that the maternal uniparental disomy 7 is responsible for the Silver–Russell syndrome (SRS) whose effects include pre- and postnatal growth retardation and other dysmorphologies. The human homologue GRB10 on chromosome 7q11.2–12 is a candidate Gene for Silver–Russell syndrome.
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Identification of the Meg1/Grb10 Imprinted Gene on mouse proximal chromosome 11, a candidate for the Silver–Russell syndrome Gene
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Naoki Miyoshi, Takashi Kohda, Yoshimi Kuroiwa, Hiroshi Shitara, Hiromichi Yonekawa, Tohru Kawabe, Hideaki Hasegawa, Sheilla C Barton, M. Azim Surani, Tomoko Kaneko-ishinoAbstract:In a systematic screen for maternally expressed Imprinted Genes using subtraction hybridization with androGenetic and normal fertilized mouse embryos, seven candidate maternally expressed Genes (Megs) have been isolated, including the H19 and p57Kip2 Genes that are known to be maternally expressed. Herein, we demonstrate that an Imprinted Gene, Meg1, is apparently identical to Grb10 (growth factor receptor-bound protein 10), which is located on mouse proximal chromosome 11. Grb10 protein was reported to bind to the insulin receptor and/or the insulin-like growth factor (IGF) I receptor via its src homology 2 domain and to inhibit the associated tyrosine kinase activity that is involved in the growth promoting activities of insulin and IGFs (IGF-I and -II). Thus, it is probable that Meg1/Grb10 is responsible for the Imprinted effects of prenatal growth retardation or growth promotion caused by maternal or paternal duplication of proximal chromosome 11 with reciprocal deficiencies (MatDp.prox11 or PatDp.prox11), respectively. In the human, it has been reported that the maternal uniparental disomy 7 is responsible for the Silver–Russell syndrome (SRS) whose effects include pre- and postnatal growth retardation and other dysmorphologies. The human homologue GRB10 on chromosome 7q11.2–12 is a candidate Gene for Silver–Russell syndrome.
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human peg1 mest an Imprinted Gene on chromosome 7
Human Molecular Genetics, 1997Co-Authors: Shin Kobayashi, Takashi Kohda, Naoki Miyoshi, Yoshimi Kuroiwa, Kohzo Aisaka, Osamu Tsutsumi, Tomoko Kanekoishino, Fumitoshi IshinoAbstract:: The mouse Peg1/Mest Gene is an Imprinted Gene that is expressed particularly in mesodermal tissues in early embryonic stages. It was the most abundant Imprinted Gene among eight paternally expressed Genes (Peg 1-8) isolated by a subtraction-hybridization method from a mouse embryonal cDNA library. It has been mapped to proximal mouse chromosome 6, maternal duplication of which causes early embryonic lethality. The human chromosomal region that shares syntenic homology with this is 7q21-qter, and human maternal uniparental disomy 7 (UPD 7) causes apparent growth deficiency and slight morphological abnormalities. Therefore, at least one paternally expressed Imprinted Gene seems to be present in this region. In this report, we demonstrate that human PEG1/MEST is an Imprinted Gene expressed from a paternal allele and located on chromosome 7q31-34, near D7S649. It is the first Imprinted Gene mapped to human chromosome 7 and a candidate for a Gene responsible for primordial growth retardation including Silver-Russell syndrome (SRS).
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Human PEG1/MEST, an Imprinted Gene on Chromosome 7
Human Molecular Genetics, 1997Co-Authors: Shin Kobayashi, Takashi Kohda, Naoki Miyoshi, Yoshimi Kuroiwa, Kohzo Aisaka, Osamu Tsutsumi, Tomoko Kaneko-ishino, Fumitoshi IshinoAbstract:: The mouse Peg1/Mest Gene is an Imprinted Gene that is expressed particularly in mesodermal tissues in early embryonic stages. It was the most abundant Imprinted Gene among eight paternally expressed Genes (Peg 1-8) isolated by a subtraction-hybridization method from a mouse embryonal cDNA library. It has been mapped to proximal mouse chromosome 6, maternal duplication of which causes early embryonic lethality. The human chromosomal region that shares syntenic homology with this is 7q21-qter, and human maternal uniparental disomy 7 (UPD 7) causes apparent growth deficiency and slight morphological abnormalities. Therefore, at least one paternally expressed Imprinted Gene seems to be present in this region. In this report, we demonstrate that human PEG1/MEST is an Imprinted Gene expressed from a paternal allele and located on chromosome 7q31-34, near D7S649. It is the first Imprinted Gene mapped to human chromosome 7 and a candidate for a Gene responsible for primordial growth retardation including Silver-Russell syndrome (SRS).
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peg1 mest Imprinted Gene on chromosome 6 identified by cdna subtraction hybridization
Nature Genetics, 1995Co-Authors: Tomoko Kanekoishino, Takashi Kohda, Naoki Miyoshi, Yoshimi Kuroiwa, Fumitoshi Ishino, Sheila C Barton, Stephane Viville, R Suzuki, Minesuke Yokoyama, M A SuraniAbstract:ParthenoGenesis in the mouse is embryonic lethal partly because of Imprinted Genes that are expressed only from the paternal genome. In a systematic screen using subtraction hybridization between cDNAs from normal and parthenoGenetic embryos, we initially identified two apparently novel Imprinted Genes, Peg1 and Peg3. Peg1 (paternally expressed Gene 1) or Mest, the first Imprinted Gene found on the mouse chromosome 6, may contribute to the lethality of parthenogenones and of embryos with a maternal duplication for the proximal chromosome 6. Peg1/Mest is widely expressed in mesodermal tissues and belongs to the alpha/beta hydrolase fold family. A similar approach with androgenones can be used to identify Imprinted Genes that are expressed from the maternal genome only.
