Lack of involvement of known DNA methyltransferases in familial hydatidiform mole implies the involvement of other factors in establishment of imprinting in the human female germline

Hayward, Bruce E.; Vos, M. De; Judson, Hannah; Hodge, Donald; Huntriss, John; Picton, Helen M.; Sheridan, Eamonn; Bonthron, David T.

doi:10.1186/1471-2156-4-2

Cited by 41 publications

(8 citation statements)

References 33 publications

(33 reference statements)

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“…Here, we show that embryos derived from oocytes lacking Dnmt3L (and, therefore, unable to establish primary maternal methylation imprints) had a paternal-specific epigenotype on both parental alleles at all Gnas DMRs, confirming that Gnas imprinting depends on one or more maternal primary imprint marks. A similar effect on GNAS imprinting was also found in human biparental complete hydatidiform moles (23), in which primary maternal methylation imprints fail to be established by other unknown mechanisms (24). However, unlike the mouse embryos, the moles had a biparental pattern of random and partial methylation of the Gnasxl first exon, reminiscent of the pattern observed in this region in normal mouse blastocysts (6).…”

Section: Discussionsupporting

confidence: 54%

Identification of the control region for tissue-specific imprinting of the stimulatory G protein α-subunit

Liu

Chen

Deng

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Gnas is a complex gene with multiple imprinted promoters. The upstream Nesp and Nespas͞Gnasxl promoters are paternally and maternally methylated, respectively. The downstream promoter for the stimulatory G protein ␣-subunit (Gs␣) is unmethylated, although in some tissues (e.g., renal proximal tubules), G s␣ is poorly expressed from the paternal allele. Just upstream of the Gs␣ promoter is a primary imprint mark (1A region) where maternalspecific methylation is established during oogenesis. Pseudohypoparathyroidism type 1B, a disorder of renal parathyroid hormone resistance, is associated with loss of 1A methylation. Analysis of embryos of Dnmt3L ؊/؊ mothers (which cannot methylate maternal imprint marks) showed that Nesp, Nespas͞Gnasxl, and 1A imprinting depend on one or more maternal primary imprint marks. We generated mice with deletion of the 1A differentially methylated region. These mice had normal Nesp-Nespas͞Gnasxl imprinting, indicating that the Gnas locus contains two independent imprinting domains (Nespas-Nespas͞Gnasxl and 1A-G s␣) controlled by distinct maternal primary imprint marks. Paternal, but not maternal, 1A deletion resulted in Gs␣ overexpression in proximal tubules and evidence for increased parathyroid hormone sensitivity but had no effect on G s␣ expression in other tissues where Gs␣ is normally not imprinted. The 1A region is a maternal imprint mark that contains one or more methylation-sensitive cis-acting elements that suppress Gs␣ expression from the paternal allele in a tissue-specific manner.genomic imprinting ͉ pseudohypoparathyroidism ͉ DNA methylation ͉ guanine nucleotide binding protein

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Section: Discussionsupporting

confidence: 54%

Identification of the control region for tissue-specific imprinting of the stimulatory G protein α-subunit

Liu

Chen

Deng

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…However, the maternal genomes of the inherited biparental moles appear to lack methylation imprints (and, thus, look and act more like paternal genomes or have a paternal 'epigenotype') as a result of a postulated defect in the female germ line (Judson et al 2002). The defect in the female germ line is not likely to be due to a defect in one of the DNMTs because no mutations were detected (Hayward et al 2003). It is possible that an as yet unidentified factor, such as a protein or an enzyme, involved in regulating the establishment of imprints is affected; identifying the factor may shed new light on imprint establishment mechanisms in humans, as well as other species.…”

Section: Epigenetics Genomic Imprinting and The Germ Line: Implicatimentioning

confidence: 99%

Gamete imprinting: setting epigenetic patterns for the next generation

Trasler¹

2006

Reprod. Fertil. Dev.

120

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Abstract. The acquisition of genomic DNA methylation patterns, including those important for development, begins in the germ line. In particular, imprinted genes are differentially marked in the developing male and female germ cells to ensure parent-of-origin-specific expression in the offspring. Abnormalities in imprints are associated with perturbations in growth, placental function, neurobehavioural processes and carcinogenesis. Based, for the most part, on data from the well-characterised mouse model, the present review will describe recent studies on the timing and mechanisms underlying the acquisition and maintenance of DNA methylation patterns in gametes and early embryos, as well as the consequences of altering these patterns.

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“…FBHM conceptuses are similar in clinical presentation to spontaneous androgenetic complete hydatidiform moles despite the biparental inheritance of the chromosome complement. At least two loci that independently cause FBHM have been mapped to moderate resolution (96)(97)(98).…”

mentioning

confidence: 99%

Eukaryotic Cytosine Methyltransferases

Goll

Bestor

2005

Annu. Rev. Biochem.

1,868

1,507

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Large-genome eukaryotes use heritable cytosine methylation to silence promoters, especially those associated with transposons and imprinted genes. Cytosine methylation does not reinforce or replace ancestral gene regulation pathways but instead endows methylated genomes with the ability to repress specific promoters in a manner that is buffered against changes in the internal and external environment. Recent studies have shown that the targeting of de novo methylation depends on multiple inputs; these include the interaction of repeated sequences, local states of histone lysine methylation, small RNAs and components of the RNAi pathway, and divergent and catalytically inert cytosine methyltransferase homologues that have acquired regulatory roles. There are multiple families of DNA (cytosine-5) methyltransferases in eukaryotes, and each family appears to be controlled by different regulatory inputs. Sequence-specific DNA-binding proteins, which regulate most aspects of gene expression, do not appear to be involved in the establishment or maintenance of genomic methylation patterns.

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Lack of involvement of known DNA methyltransferases in familial hydatidiform mole implies the involvement of other factors in establishment of imprinting in the human female germline

Cited by 41 publications

References 33 publications

Identification of the control region for tissue-specific imprinting of the stimulatory G protein α-subunit

Identification of the control region for tissue-specific imprinting of the stimulatory G protein α-subunit

Gamete imprinting: setting epigenetic patterns for the next generation

Eukaryotic Cytosine Methyltransferases

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