Loss of the maternal imprint in Dnmt3L mice leads to a differentiation defect in the extraembryonic tissue

Arima, Takahiro; Hata, Kenichiro; Tanaka, Satoshi; Kusumi, Maki; Li, En; Kato, Kanefusa; Shiota, Kunio; Sasaki, Hidetada; Wake, Norio

doi:10.1016/j.ydbio.2006.05.003

Cited by 91 publications

(72 citation statements)

References 42 publications

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“…40,41 Specific genetic approaches have shown that lack of DNMT1 or DNMT3L genes results in impaired trophoblast differentiation and aberrant placenta development. 42,43 A recent report has revealed that LINE-1 sequences are significantly hypermethylated in partial hydatidiform moles tissues Figure 3 DNMT1 (a), DNMT3a (b) and DNMT3b (c) mRNA levels in placentas were determined by real-time PCR. The expression of DNMTs was normalized by the control genes GAPDH and b-actin.…”

Section: Discussionmentioning

confidence: 99%

Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas

et al. 2011

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Preeclampsia (PE) is a severe hypertensive disorder associated with pregnancy; despite substantial research effort in the past several years, the etiology of PE is still unclear. The role of epigenetic factors in the etiology of PE, including DNA methylation, has been poorly characterized. In the present study, we investigated global DNA methylation as well as DNA methylation of the paternally imprinted H19 gene in preeclamptic placentas. Using 5-methylcytosine immunohistochemistry and Alu and LINE-1 repeat pyrosequencing, we found that the global DNA methylation level and the DNA (cytosine-5) methyltransferase 1 mRNA level were significantly higher in the early-onset preeclamptic placentas when compared with the normal controls. Data from methylation-sensitive high resolution melting demonstrated hypermethylation of the promoter region of the H19 gene, and results of real-time PCR showed decreased mRNA expression of H19 gene in the early-onset preeclamptic placentas as compared with the normal controls. Our results suggest that abnormal DNA methylation during placentation might be involved in the pathophysiology of PE, especially early-onset preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas

et al. 2011

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“…Mutations in several imprinted genes affect the trophoblast exclusivley (Coan et al, 2005;Kaneko-Ishino et al, 2003). Defects in the trans-acting machinery that regulates imprinting, such as DNA methyltransferase deficiency (Lei et al, 1996;Bourc'his et al, 2001;Hata et al, 2002;Kaneda et al, 2004;Arima et al, 2006) or mutations causing familial hydatidiform moles (Judson et al, 2002;Murdoch et al, 2006) result in abnormal placentation. Finally, interspecific hybrids (Vrana et al, 1998;Vrana et al, 2000), somatic cell nuclear transfer embryos (Dindot et al, 2004;Inoue et al, 2002) and uniparental embryos (Surani et al, 1986;Varmuza et al, 1993;Mann 2005) all suffer from dysmorphic trophoblast, in part or in whole because of abnormal expression of imprinted genes.…”

Section: Sfmbt2 and Yy1 Interact In Mammalian Cellsmentioning

confidence: 99%

The PcG gene Sfmbt2 is paternally expressed in extraembryonic tissues

Kuzmin

Han

Golding

et al. 2008

Gene Expression Patterns

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Genomic imprinting has dramatic effects on placental development, as has been clearly observed in interspecific hybrid, somatic cell nuclear transfer, and uniparental embryos. In fact, the earliest defects in uniparental embryos are evident first in the extraembryonic trophoblast. We performed a microarray comparison of gynogenetic and androgenetic mouse blastocysts, which are predisposed to placental pathologies, to identify imprinted genes. In addition to identifying a large number of known imprinted genes, we discovered that the Polycomb group (PcG) gene Sfmbt2 is imprinted. Sfmbt2 is expressed preferentially from the paternal allele in early embryos, and in later stage extraembryonic tissues. A CpG island spanning the transcriptional start site is differentially methylated on the maternal allele in e14.5 placenta. Sfmbt2 is located on proximal chromosome 2, in a region known to be imprinted, but for which no genes had been identified until now. This possibly identifies a new imprinted domain within the murine genome. We further demonstrate that murine SFMBT2 protein interacts with the transcription factor YY1, similar to the Drosophila PHO-RC. KeywordsGenomic Imprinting; Sfmbt2; PcG gene; Extraembryonic tissues; placenta; MMU2; YY1; microarrays; uniparental embryos Results and DiscusssionThe role played by imprinted genes in placental development is gaining wider attention as the impact of imprinting disruptions on placental pathology is explored. Both hyper-and hypoplastic placentation are linked to imprinted gene function (Kanayama et al., 2002;Murdoch et al., 2006; reviewed in Kaneko-Ishino et al., 2003). The most dramatic example of this is diploid, uniparental embryos. Gynogenetic embryos (two maternal/no paternal genomes) and androgenetic embryos (two paternal/no maternal genomes) both exhibit defects in the earliest differentiated tissue in mammals, the extraembryonic trophoblast (Barton et al., 1984;McGrath and Solter, 1984;Mann, 2005). At mid-gestation, gynogenetic embryos possess only a few residual trophoblast giant cells while androgenetic embryos are characterized by a mass of hypertrophic trophoblast. These observations indicate that a suite of genes required * Corresponding author. s.varmuza@utoronto.ca; tel. 1-416-978-2759; FAX 1-416-978-8532. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptGene Expr Patterns. Author manuscript; available in PMC 2009 January 1. Published in final edited form as:Gene Expr Patterns. 2008 January ; 8(2): 107-116. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manu...

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“…DNA methylation is a mechanism by which genes can be silenced and is important for the epigenetic regulation of placental development (37). Therefore, we sought to determine if the lack of XAF1 expression in first trimester trophoblasts was due to the methylation of the XAF1 promoter.…”

Section: Xaf1-induced Xiap Cleavage Is Both Caspase-and Omi-independementioning

confidence: 99%

XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway

Chavez

Visintin

Karassina

et al. 2007

Journal of Biological Chemistry

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Tumor necrosis factor-␣ (TNF-␣) and Fas ligand induce apoptosis by interacting with their corresponding membranebound death receptors and activating caspases. Since both systems share several components of the intracellular apoptotic cascade and are expressed by first trimester trophoblasts, it is unknown how these cells remain resistant to Fas ligand while sensitive to TNF-␣. XAF1 (X-linked inhibitor of apoptosis (XIAP)-associated factor 1) is a proapoptotic protein that antagonizes the caspase-inhibitory activity of XIAP. Here, we demonstrated that XAF1 functions as an alternative pathway for TNF-␣-induced apoptosis by translocating to the mitochondria and promoting XIAP inactivation. In addition, we showed that the overexpression of XAF1 sensitized first trimester trophoblast cells to Fas-mediated apoptosis. Furthermore, we also determined that the differential expression of XAF1 in first and third trimester trophoblast cells was due to changes in XAF1 gene methylation. Our results establish a novel regulatory pathway controlling trophoblast cell survival and provide a molecular mechanism to explain trophoblast sensitivity to TNF-␣ and the increased number of apoptotic trophoblast cells observed near term. Aberrant XAF1 expression and/or localization may have consequences for normal pregnancy outcome.

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Loss of the maternal imprint in Dnmt3L mice leads to a differentiation defect in the extraembryonic tissue

Cited by 91 publications

References 42 publications

Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas

Detection of global DNA methylation and paternally imprinted H19 gene methylation in preeclamptic placentas

The PcG gene Sfmbt2 is paternally expressed in extraembryonic tissues

XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway

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