Disease relevance of Genomic Imprinting

• Maintenance of genomic imprinting at the IGF2 locus in hepatoblastoma [1].
• The necdin and MAGEL2 genes are subjected to genomic imprinting and suggested to be involved in the etiology of Prader-Willi syndrome [2].
• Expression and parental imprinting of the H19 gene in human rhabdomyosarcoma [3].
• In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases [4].
• To establish a possible role of genomic imprinting in the carcinogenesis of epithelial ovarian cancer, we determined the imprinting status of both IGF-II and H19 genes in 43 ovarian cancers, 7 low malignant potential ovarian tumors, and their matched normal tissues [5].

High impact information on Genomic Imprinting

• Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene [6].
• The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mice [7].
• Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse [8].
• In this study using uniparental embryos, we demonstrate that Xist expression is initially dictated solely by parental imprinting, causing expression of all paternal alleles [9].
• Our results demonstrate parental imprinting of Mas and suggest that the maternally inherited allele is transcriptionally repressed in a developmental and tissue-specific manner [10].

Chemical compound and disease context of Genomic Imprinting

• This defect was not reversible after treatment (normalization of blood glucose) and is therefore a candidate for the primary defect which is likely to be of genetic origin, but also could be caused by genetic imprinting, intrauterine malnutrition and social inheritance (obesity) [11].

Biological context of Genomic Imprinting

• The functional significance of DNA methylation in genomic imprinting was strengthened by the recent finding that CpG islands (or sites) in three imprinted genes, H19, insulin-like growth factor 2 (Igf-2), and Igf-2 receptor (Igf-2r), are differentially methylated depending on their parental origin [12].
• Recent studies have focused on the effects of histone acetylation on gene expression regulation during development and the roles of histone hypoacetylation in the maintenance of centromeric structure, X-inactivation and genomic imprinting [13].
• The mouse insulin-like growth factor II (Igf2) gene, which is located on distal chromosome 7 (Chr7), has been shown previously to undergo tissue-specific parental imprinting [14].
• Mendel stayed home. Genomic imprinting and environmental disease susceptibility, National Institute of Environmental Health Sciences and Duke University Medical Center, Durham, NC, USA, 8-10 October 1998 [15].
• Inverse relationship between age at onset of Huntington disease and paternal age suggests involvement of genetic imprinting [16].

Anatomical context of Genomic Imprinting

• To explore the molecular mechanism of maintenance of genomic imprinting, we targeted the region between insulin 2 and Igf2, where the cis imprint maintenance element (IME) resides in mouse fibroblasts [17].
• In contrast, choroid plexus and leptomeninges express IGF-II mRNAs biallelically, indicating that cell type-specific regulation of genomic imprinting occurs within the mammalian CNS [18].
• To determine if this component of genomic imprinting is also found in marsupials, Dnmt1 isoforms were examined in somatic cells and germ cells of the South American opossum Monodelphis domestica [19].
• The gene MEST (or PEG1) on chromosome 7q32 is paternally expressed in human fetal tissues as a result of genomic imprinting [20].
• Analysis of NT and control pregnancies indicated disruption of genomic imprinting at the X inactivation-specific transcript (XIST) locus in the chorion, but not the fetus of clones, whereas proper allelic expression of the insulin-like growth factor II (IGF2) and gene trap locus 2 (GTL2) loci was maintained in both the fetus and placenta [21].

Associations of Genomic Imprinting with chemical compounds

• Genomic imprinting. Silence across the border [22].
• Genomic imprinting. Action at a distance [23].
• Global genome demethylation caused by targeted mutations in the DNA methyltransferase-1 (Dnmt1) gene has shown that cytosine methylation plays essential roles in X-inactivation, genomic imprinting and genome stabilization [24].
• Genomic imprinting contributes to thyroid hormone metabolism in the mouse embryo [25].
• Modulation of Igf2 genomic imprinting in mice induced by 5-azacytidine, an inhibitor of DNA methylation [26].

Gene context of Genomic Imprinting

• Genetic analysis of genomic imprinting: an Imprintor-1 gene controls inactivation of the paternal copy of the mouse Tme locus [27].
• Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene [14].
• The implications of these findings for the function of DNMT3L and Dnmt3a in DNA methylation and genomic imprinting are discussed [28].
• Our experiments confirm that Grb10 is subject to genomic imprinting with the majority of Grb10 expression arising from the maternally inherited allele [29].
• H19, which has become a model for genomic imprinting, was identified initially in a screen for Afr1-regulated genes [30].

References