IGF2 is parentally imprinted in human preimplantation embryos

Lighten, Antony D.; Hardy, Kate; Winston, R. M. L.; Moore, Gudrun E.

doi:10.1038/ng0297-122

Cited by 43 publications

(39 citation statements)

References 15 publications

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“…This is in agreement with our study of imprinted genes in sheep blastocysts, where nine genes examined exhibited monoallelic expression only post-implantation (Thurston et al 2008). A gene-specific, temporal imprinting pattern has also been suggested by the observation of both monoallelically and biallelically expressed imprinted genes in human (Lighten et al 1997;Ray et al 1997;Huntriss et al 1998;Monk and Salpekar 2001;Salpekar et al 2001), mouse (Szabo and Mann 1995;Rossant et al 1998), and bovine (Ruddock et al 2004) blastocysts. However, while it is tempting to speculate that the allelic expression status (i.e., monoallelic or biallelic) we ascertain for the majority of hESC lines tested represents the norm of the inner cell mass cells of the human blastocyst for each gene, in the absence of data of the allelic status for most genes in the human blastocyst, we cannot exclude the possibility that the majority of lines we have evaluated are in fact abnormal at a particular locus.…”

Section: Discussionsupporting

confidence: 80%

“…Data from the mouse embryo have suggested that some imprints are not fully established until the time of implantation (Szabo and Mann 1995;Rossant et al 1998) and this has been corroborated in the human. Although only a few imprinted genes have been examined to date in human preimplantation embryos, SNRPN (Huntriss et al 1998), MEST (previously known as PEG1) , and IGF2 (Lighten et al 1997) show monoallelic expression at this stage, whereas H19 and XIST (Ray et al 1997;Monk and Salpekar 2001) are only monoallelically expressed in postimplantation tissues (Morison et al 2005). Thus we examined the methylation status of a range of imprinted gene regulatory regions in order to investigate the role of this epigenetic modification in regulating genomic imprints in hESC.…”

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confidence: 99%

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Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines

Kim

Thurston²,

Mummery³

et al. 2007

Genome Res.

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Disregulation of imprinted genes can be associated with tumorigenesis and altered cell differentiation capacity and so could provide adverse outcomes for stem cell applications. Although the maintenance of mouse and primate embryonic stem cells in a pluripotent state has been reported to disrupt the monoallelic expression of several imprinted genes, available data have suggested relatively higher imprint stability in the human equivalents. Identification of 202 heterozygous loci allowed us to examine the allelic expression of 22 imprinted genes in 22 human embryonic stem cell lines. Half of the genes examined (IPW, H19, MEG3, MEST isoforms 1 and 2, PEG10, MESTIT1, NESP55, ATP10A, PHLDA2, IGF2) showed variable allelic expression between lines, indicating vulnerability to disrupted imprinting. However, seven genes showed consistent monoallelic expression (NDN, MAGEL2, SNRPN, PEG3, KCNQ1, KCNQ1OT1, CDKN1C). Furthermore, four genes known to be monoallelic or to exhibit polymorphic imprinting in later-developing human tissues (TP73, IGF2R, WT1, SLC22A18) were always biallelic in hESCs. MEST isoform 1, PEG10, and NESP55 showed an association between the variability observed in interline allelic expression status and the DNA methylation of previously identified regulatory regions. Our results demonstrate gene-specific differences in the stability of imprinted loci in human embryonic stem cells and identify disrupted DNA methylation as one potential mechanism. We conclude the prudence of including comprehensive imprinting analysis in the continued characterization of human embryonic stem cell lines.

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines

Kim

Thurston²,

Mummery³

et al. 2007

Genome Res.

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“…H19 is unmethylated in fetal gonocytes, and methylated in spermatogonia, spermatozoa and preimplantation embryos. IGF2 shows monoallelic expression in the human blastocyst, indicating that differential methylation is at least complete by this stage (Lighten et al 1997). Kerjean et al (2000) also showed that some paternal imprints are established during human spermatogenesis.…”

Section: Reprogramming Of Imprints In the Human Germlinementioning

confidence: 98%

Epigenetics and the germline

Allegrucci¹,

Thurston²,

Lucas³

et al. 2005

Reproduction

200

125

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Epigenetic processes affect three stages of germline development, namely (1) specification and formation of primordial germ cells and their germline derivatives through lineage-specific epigenetic modifications, in the same manner as other embryonic lineages are formed, (2) a largely genome-wide erasure and re-establishment of germline-specific epigenetic modifications that only occurs in the embryonic primordial germ cell lineage, followed by re-establishment of sex-specific patterns during gametogenesis, and (3) differential epigenetic modifications to the mature male and female gamete genomes shortly after fertilisation. This review will detail current knowledge of these three processes both at the genome-wide level and at specific imprinted loci. The consequences of epigenetic perturbation are discussed and new in vitro models which may allow further understanding of a difficult developmental period to study, especially in the human, are highlighted.

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“…To date, the imprinting status of only two genes has been established for human preimplantation development revealing that IGF2 and SNRPN are imprinted. 43,44 MEST gene transcripts are known to be expressed in human oocytes and preimplantation embryos. 38 However, earlier attempts at characterising the imprinting status of MEST in human cleavage stage embryos were inconclusive (described in Monk and Salpekar (2001) 45 ).…”

Section: Discussionmentioning

confidence: 99%

Variable imprinting of the MEST gene in human preimplantation embryos

et al. 2012

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There is evidence that expression and methylation of the imprinted paternally expressed gene 1/mesoderm-specific transcript homologue (PEG1/MEST) gene may be affected by assisted reproductive technologies (ARTs) and infertility. In this study, we sought to assess the imprinting status of the MEST gene in a large cohort of in vitro-derived human preimplantation embryos, in order to characterise potentially adverse effects of ART and infertility on this locus in early human development. Embryonic genomic DNA from morula or blastocyst stage embryos was screened for a transcribed AflIII polymorphism in MEST and imprinting analysis was then performed in cDNA libraries derived from these embryos. In 10 heterozygous embryos, MEST expression was monoallelic in seven embryos, predominantly monoallelic in two embryos, and biallelic in one embryo. Screening of cDNA derived from 61 additional human preimplantation embryos, for which DNA for genotyping was unavailable, identified eight embryos with expression originating from both alleles (biallelic or predominantly monoallelic). In some embryos, therefore, the onset of imprinted MEST expression occurs during late preimplantation development. Variability in MEST imprinting was observed in both in vitro fertilization and intracytoplasmic sperm injection-derived embryos. Biallelic or predominantly monoallelic MEST expression was not associated with any one cause of infertility. Characterisation of the main MEST isoforms revealed that isoform 2 was detected in early development and was itself variably imprinted between embryos. To our knowledge, this report constitutes the largest expression study to date of genomic imprinting in human preimplantation embryos and reveals that for some imprinted genes, contrasting imprinting states exist between embryos.

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IGF2 is parentally imprinted in human preimplantation embryos

Cited by 43 publications

References 15 publications

Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines

Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines

Epigenetics and the germline

Variable imprinting of the MEST gene in human preimplantation embryos

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