Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis

Chaillet, J. Richard; Vogt, Thomas; Beier, David R.; Leder, Philip

doi:10.1016/0092-8674(91)90140-t

Cited by 235 publications

(164 citation statements)

References 26 publications

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“…That is, it could be assembled in different patterns in the male and female germ lines by virtue of testis-or ovary-specific DNA methylases. The parentalspecific methylation must be maintained through the period after fertilization when genome-wide demethylation of nonimprinted genes has been demonstrated (Monk et al 1987;Chaillet et al 1991;Kafri et al 1992). The difference could be maintained through many somatic cell divisions through the action of DNA methyltransferase, whose substrate is hemimethylated DNA (Gruenbaum et al 1982;Bestor and Ingram 1983).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic mechanisms underlying the imprinting of the mouse H19 gene.

Bartolomei¹,

Webber²,

Brunkow³

et al. 1993

Genes Dev.

456

328

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The expression of the H19 gene is governed by parental imprinting in mammals. H19, an unusual gene encoding an RNA with no known function, is exclusively expressed from the maternal chromosome. In mouse, it lies 90 kb downstream from the lgf2 gene, which encodes a fetal-specific growth factor, insulin-like growth factor II, and is expressed primarily from the paternally inherited chromosome. In this report we have utilized interspecific hybrid mice to identify male-specific DNA methylation of a 7-to 9-kb domain surrounding the 1-119 gene and its promoter. This allele-specific methylation could function as a mark to suppress transcription of the H19 paternal allele. Consistent with this proposal, the H19 promoter displayed an open chromatin conformation only on the relatively unmethylated active maternal allele. In contrast, a cell type-specific enhancer that lies outside the methylation domain is hypersensitive to restriction enzyme digestion in nuclei on both maternal and paternal chromosomes. That the allele-specific methylation domain, coupled to the two H19 enhancers, contains all the information necessary for its imprinting was tested by examining two transgenic lines containing an internally deleted H19 transgene. Both displayed paternal-specific methylation of the transgene and maternal-specific expression. Although neither line has been tested in an inbred genetic background, and therefore the action of complex modifiers cannot be formally excluded, the result suggests that the sequences necessary for the imprinting of H19 have been identified.

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Section: Discussionmentioning

confidence: 99%

Epigenetic mechanisms underlying the imprinting of the mouse H19 gene.

Bartolomei¹,

Webber²,

Brunkow³

et al. 1993

Genes Dev.

456

328

View full text Add to dashboard Cite

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“…Alternatively, DNA m germ cells may initially undergo de novo methylation together with somatic cells but then become demethylated again prior to 12.5 days p.c. In any event, it appears that early primordial germ cells must retain the ability to demethylate DNA, because at least one imprinted transgene has been shown to erase its methylation pattern at this stage of development (Chaillet et al 1991). Monk et al (1987) have suggested previously that there is a basic difference between methylation kinetics in the male and female germ cells.…”

Section: Formation Of the Gametic Miethylation Patternsmentioning

confidence: 99%

Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line.

Kafri¹,

Ariel²,

Brandeis³

et al. 1992

Genes Dev.

688

428

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Methylation patterns of specific genes have been studied by polymerase chain reaction and found to undergo dynamic changes in the germ line and early embryo. Some CpG sites are methylated in sperm DNA and unmodified in mature oocytes, indicating that the parental genomes have differential methylation profiles. These differences, however, are erased by a series of early embryonic demethylation and postblastula remodification events, which serve to reestablish the basic adult methylation pattern prior to organogenesis. During gametogenesis, all of these sites are unmethylated in primordial germ cells but eventually become remodified by 18.5 days postcoitum in both males and females. The final methylation profile of the mature germ cells is then formed by a multistep process of site-specific demethylation events. These results form a basis for the understanding of the biochemical mechanisms and role of DNA methylation in embryonic development.

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“…DNA methylation patterns are established during early embryogenesis and gametogenesis, and are maintained in somatic cells thereafter (5). The DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b catalyze methylation of CpG dinucleotides in genomic DNA (6)(7)(8).…”

mentioning

confidence: 99%