Identification of the mouse paternally expressed imprinted gene Zdbf2 on chromosome 1 and its imprinted human homolog ZDBF2 on chromosome 2

Kobayashi, Hisato; Yamada, Kaori; Morita, Shinnosuke; Hiura, Hitoshi; Fukuda, Atsushi; Kagami, Masayo; Ogata, Tsutomu; Hata, Kenichiro; Sotomaru, Yusuke; Kono, Toru

doi:10.1016/j.ygeno.2008.12.012

Cited by 63 publications

(59 citation statements)

References 54 publications

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“…Zdbf2 could be one such example. Zdbf2 is detected in our data to be imprinted with preferential paternal expression, but it has been previously reported to be biallelically expressed in the placenta (Kobayashi et al 2009). However, this could also be due to a different imprinting status of the same gene in different developmental stages/mouse strain combinations.…”

Section: Assessment Of the Degree Of Maternal Contamination In Our Plcontrasting

confidence: 60%

“…Ndn (MacDonald and Wevrick 1997) and Magel2 (Boccaccio et al 1999) are both expressed in the mouse placenta, whereas the imprinting status was not clear. Rian (Hatada et al 2001), Zim1 (Kim et al 1999), Meg3 (Miyoshi et al 2000), Mirg (Seitz et al 2004), Usp29 (Kim et al 2000), Impact (Hagiwara et al 1997), Nnat (Kagitani et al 1997), Zdbf2 (Kobayashi et al 2009), and Zrsr1 (Hatada et al 1993) were not previously reported to be imprinted in the mouse placenta either. Therefore, we identified 12 candidate genes with novel mouse placenta imprinting status.…”

Section: Detection Of Significant Parent-of-origin Effectsmentioning

confidence: 96%

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A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq

2011

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Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on embryonic day 17.5 (E17.5) mouse placenta cDNA samples from reciprocal cross F 1 progeny of AKR and PWD mouse strains and quantified the allele-specific expression and the degree of parent-of-origin allelic imbalance. We confirmed the imprinting status of 23 known imprinted genes in the placenta and found that 12 genes reported previously to be imprinted in other tissues are also imprinted in mouse placenta. Through a wellreplicated design using an orthogonal allelic-expression technology, we verified 5 novel imprinted genes that were not previously known to be imprinted in mouse (Pde10, Phf17, Phactr2, Zfp64, and Htra3). Our data suggest that most of the strongly imprinted genes have already been identified, at least in the placenta, and that evidence supports perhaps 100 additional weakly imprinted genes. Despite previous appearance that the placenta tends to display an excess of maternally expressed imprinted genes, with the addition of our validated set of placenta-imprinted genes, this maternal bias has disappeared.

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Section: Assessment Of the Degree Of Maternal Contamination In Our Plcontrasting

confidence: 60%

Section: Detection Of Significant Parent-of-origin Effectsmentioning

confidence: 96%

A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq

2011

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“…At the molecular level, imprints are characterised by epigenetic modifications Sasaki and Matsui, 2008), which include DNA methylation: imprinted genes are associated with differentially methylated regions (DMRs) that are methylated on either the paternal or maternal allele. In the mouse, 21 DMRs (of which four are paternally methylated and 17 are maternally methylated) are known to acquire methylation in the gametes (primary DMRs) (Chotalia et al, 2009;Kobayashi et al, 2009), and many of them have been shown to constitute imprint centres (ICs) that regulate nearby imprinted genes in cis (Wutz et al, 1997;Thorvaldsen et al, 1998;Fitzpatrick et al, 2002;Yoon et al, 2002;Lin et al, 2003;Williamson et al, 2004;Shiura et al, 2009). The methylation marks of such primary DMRs are presumed to be maintained throughout embryonic development, including during the preimplantation stages at which extensive demethylation of the genome takes place, but few have been examined in detail throughout development .…”

Section: Introductionmentioning

confidence: 99%

Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes

et al. 2011

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SUMMARYMammalian imprinted genes are associated with differentially methylated regions (DMRs) that are CpG methylated on one of the two parental chromosomes. In mice, at least 21 DMRs acquire differential methylation in the germline and many of them act as imprint centres. We previously reported the physical extents of differential methylation at 15 DMRs in mouse embryos at 12.5 days postcoitum. To reveal the ontogeny of differential methylation, we determined and compared methylation patterns of the corresponding regions in sperm and oocytes. We found that the extent of the gametic DMRs differs significantly from that of the embryonic DMRs, especially in the case of paternal gametic DMRs. These results suggest that the gametic DMR sequences should be used to extract the features specifying methylation imprint establishment in the germline: from this analysis, we noted that the maternal gametic DMRs appear as unmethylated islands in male germ cells, which suggests a novel component in the mechanism of gamete-specific marking. Analysis of selected DMRs in blastocysts revealed dynamic changes in allelic methylation in early development, indicating that DMRs are not fully protected from the major epigenetic reprogramming events occurring during preimplantation development. Furthermore, we observed non-CpG methylation in oocytes, but not in sperm, which disappeared by the blastocyst stage. Non-CpG methylation was frequently found at maternally methylated DMRs as well as non-DMR regions, suggesting its prevalence in the oocyte genome. These results provide evidence for a unique methylation profile in oocytes and reveal the surprisingly dynamic nature of DMRs in the early embryo.

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“…Here we report the case of a region of transient germline DMRs (gDMRs) inherited from the oocyte at the mouse Gpr1/Zdbf2 (DBF-type zinc finger-containing protein 2) locus (1qC2) (Kobayashi et al 2009). We found that this maternal gDMR coincides with a promoter, which initiates transcription of long isoforms of Zdbf2 (Liz) in a paternal-specific manner but is shut down upon DNA methylation gain after implantation.…”

mentioning

confidence: 99%

The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic imprinting in mammals

et al. 2014

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Many loci maintain parent-of-origin DNA methylation only briefly after fertilization during mammalian development: Whether this form of transient genomic imprinting can impact the early embryonic transcriptome or even have life-long consequences on genome regulation and possibly phenotypes is currently unknown. Here, we report a maternal germline differentially methylated region (DMR) at the mouse Gpr1/Zdbf2 (DBF-type zinc finger-containing protein 2) locus, which controls the paternal-specific expression of long isoforms of Zdbf2 (Liz) in the early embryo. This DMR loses parental specificity by gain of DNA methylation at implantation in the embryo but is maintained in extraembryonic tissues. As a consequence of this transient, tissue-specific maternal imprinting, Liz expression is restricted to the pluripotent embryo, extraembryonic tissues, and pluripotent male germ cells. We found that Liz potentially functions as both Zdbf2-coding RNA and cis-regulatory RNA. Importantly, Liz-mediated events allow a switch from maternal to paternal imprinted DNA methylation and from Liz to canonical Zdbf2 promoter use during embryonic differentiation, which are stably maintained through somatic life and conserved in humans. The Gpr1/Zdbf2 locus lacks classical imprinting histone modifications, but analysis of mutant embryonic stem cells reveals fine-tuned regulation of Zdbf2 dosage through DNA and H3K27 methylation interplay. Together, our work underlines the developmental and evolutionary need to ensure proper Liz/Zdbf2 dosage as a driving force for dynamic genomic imprinting at the Gpr1/Zdbf2 locus.

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Identification of the mouse paternally expressed imprinted gene Zdbf2 on chromosome 1 and its imprinted human homolog ZDBF2 on chromosome 2

Cited by 63 publications

References 54 publications

A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq

A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq

Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes

The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic imprinting in mammals

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