Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal

Stöger, Reinhard; Kubicka, Pavel; Liu, C. G.; Kafri, Tal; Razin, Aharon; Cedar, Howard; Barlow, Denise P.

doi:10.1016/0092-8674(93)90160-r

Cited by 568 publications

(196 citation statements)

References 32 publications

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“…As mentioned previously, CpG island methylation plays an active role in maintaining silencing of parentally imprinted genes (14)(15)(16)(17) and also in silencing genes on the inactivated X chromosome (13). We thus examined the expression status of the VHL gene at the RNA level in cell lines with unmethylated and abnormally methylated VHL genes.…”

Section: Resultsmentioning

confidence: 99%

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Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.

Herman

Latif

Weng

et al. 1994

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

1,350

753

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Mutational Inactivation and allelic loss of the von HlppelLlndau (VHL) gene appear to be causal events for the majority of spontaneous clear-cell renal cardnomas. We now show that hypermethylatlon of a normally unmethylated CpG Island in the 5' region provides another potentially important mechanism for Inactivation of the VHL gene In a siificant portion of these cancers. This hypermethylation was found in S of 26 (19%) tumors examined. Four of these had lost one copy of VHL while one retained two heavily methylated alleles. Four of the tumors with VHL hypermethylation had no detectable mutations, whereas one had a missense mutation In addition to hypermethylation of the single retained allele. As would be predicted for the consequence of methylation in this 5' CpG island, none of the 5 tumors expressed the VHL gene.

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Section: Resultsmentioning

confidence: 99%

“…In normal cells, CpG islands on autosomal chromosomes remain unmethylated. However, many islands on the transcriptionally inactive X chromosome (13) or in selected genes silenced by parental imprinting (14)(15)(16) are extensively methylated. The active participation of this methylation in silencing imprinted genes has recently been shown (17).…”

mentioning

confidence: 99%

Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.

Herman

Latif

Weng

et al. 1994

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

1,350

753

View full text Add to dashboard Cite

show abstract

“…This lack of allelic histone modification has been reported in a human cell line, although imprinted expression was not analyzed (22). The mouse Igf2r gene contains two DMRs: the germ-line methylated intronic region 2 ICE and the somatic DMR at the promoter CpG island of the Igf2r gene (23). Both these regions are associated with modified histones (13,14); however, in the Eed null mice, the imprinting of Igf2r is unaffected (24), suggesting that H3K27 methylation is not involved in the imprinting of this gene.…”

Section: Allelic Expression and Methylation Within The Kcnq1 Domainmentioning

confidence: 99%

Limited evolutionary conservation of imprinting in the human placenta

Monk

Arnaud

Apostolidou

et al. 2006

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

229

201

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The epigenetic phenomenon of genomic imprinting provides an additional level of gene regulation that is confined to a limited number of genes, frequently, but not exclusively, important for embryonic development. The evolution and maintenance of imprinting has been linked to the balance between the allocation of maternal resources to the developing fetus and the mother's well being. Genes that are imprinted in both the embryo and extraembryonic tissues show extensive conservation between a mouse and a human. Here we examine the human orthologues of mouse genes imprinted only in the placenta, assaying allele-specific expression and epigenetic modifications. The genes from the KCNQ1 domain and the isolated human orthologues of the imprinted genes Gatm and Dcn all are expressed biallelically in the human, from first-trimester trophoblast through to term. This lack of imprinting is independent of promoter CpG methylation and correlates with the absence of the allelic histone modifications dimethylation of lysine-9 residue of H3 (H3K9me2) and trimethylation of lysine-27 residue of H3 (H3K27me3). These specific histone modifications are thought to contribute toward regulation of imprinting in the mouse. Genes from the IGF2R domain show polymorphic concordant expression in the placenta, with imprinting demonstrated in only a minority of samples. Together these findings have important implications for understanding the evolution of mammalian genomic imprinting. Because most human pregnancies are singletons, this absence of competition might explain the comparatively relaxed need in the human for placentalspecific imprinting.histones ͉ methylation ͉ epigenetics

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“…*10 6 colonies were screened with a randomly labelled 1.5 kb mouse fra-1 cDNA as previously described (StoÈ ger et al, 1993). Four positive clones were isolated, and one of them, cosmid 22, was further characterised.…”

Section: Cloning Of Genomic Dna and Sequence Analysismentioning

confidence: 99%

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis)

et al. 1997

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We have determined the genomic structure of the mouse fra-1 gene, which consists of four exons and three introns at positions also found in the other members of the fos gene family. Fra-1 is expressed rather highly in the brain and testes of adult mice, and at low levels in most other tissues. Absence of c-Fos leads to signi®cantly reduced serum stimulation of fra-1 expression in gene targeted mouse ®broblasts, demonstrating that mitogen induction of fra-1 is partially mediated by c-Fos/AP-1. A polymorphic (CA) n microsatellite marker was found in intron 2 of fra-1 and used to map the gene to the centromeric region of mouse chromosome 19. Since fra-1 maps to the same genomic region as oc (osteosclerosis), an autosomal recessive disorder leading to the bone remodelling disease osteopetrosis, we tested it as a candidate gene for oc. The segregation of fra-1 in two di erent crosses of mice carrying oc and an allelism test between oc and a targeted disruption of fra-1 demonstrate that fra-1 and oc are two distinct genes rather than oc being a mutant allele of fra-1.

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Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal

Cited by 568 publications

References 32 publications

Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.

Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.

Limited evolutionary conservation of imprinting in the human placenta

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis)

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