Chromosome 11p15.5 regional imprinting: comparative analysis of KIP2 and H19 in human tissues and Wilms' tumors
| Autor: | Benjamin Tycko, Terrence Hensle, Luwa Yuan, Lin Feng, Wai-Yee Chung |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Heterozygote RNA Untranslated Muscle Proteins Biology Decitabine Wilms Tumor Cell Line Loss of heterozygosity Genomic Imprinting Fetus Gene expression Genetics Humans Genes Tumor Suppressor RNA Messenger Imprinting (psychology) Allele Enzyme Inhibitors Child Molecular Biology Gene Cyclin-Dependent Kinase Inhibitor p57 DNA Modification Methylases Genetics (clinical) Alleles DNA Primers Regulation of gene expression Base Sequence Chromosomes Human Pair 11 Infant Newborn Nuclear Proteins General Medicine DNA Methylation Molecular biology Kidney Neoplasms Gene Expression Regulation DNA methylation Azacitidine Female RNA Long Noncoding Genomic imprinting |
| Zdroj: | Human molecular genetics. 5(8) |
| ISSN: | 0964-6906 |
| Popis: | The imprinted H19 gene is frequently inactivated in Wilms' tumors (WTs) either by chromosome 11p15.5 loss of heterozygosity (LOH) or by hypermethylation of the maternal allele and it is possible that there might be coordinate disruption of imprinting of multiple 11p15.5 genes in these tumors. To test this we have characterized total and allele-specific mRNA expression levels and DNA methylation of the 11p15.5 KIP2 gene in normal human tissues, WTs and embryonal rhabdomyosarcoma (RMS). Both KIP2 alleles are expressed but there is a bias with the maternal allele contributing 70-90% of mRNA. Tumors with LOH show moderate to marked reductions in KIP2 mRNA relative to control tissues and residual mRNA expression is from the imprinted paternal allele. Among WTs without LOH most cases with H19 inactivation also have reduced KIP2 expression and most cases with persistent H19 expression have high levels of KIP2 mRNA. In contrast to the extensive hypermethylation of the imprinted H19 allele, both KIP2 alleles are hypomethylated and WTs with biallelic H19 hypermethylation lack comparable hypermethylation of KIP2 DNA. 5-aza-2'-deoxycytidine (aza-C) increases H19 expression in RD RMS cells but does not activate KIP2 expression. These data indicate coordinately reduced expression of two linked paternally imprinted genes in most WTs and also suggest mechanistic differences in the maintenance of imprinting at these two loci. |
| Databáze: | OpenAIRE |
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