Mechanisms of Igf2/H19 imprinting: DNA methylation, chromatin and long-distance gene regulation.
The mouse Igf2 and H19 genes lie 70-kb apart on chromosome 7 and are reciprocally imprinted. Two regulatory regions are important for their parental allele-specific expression: a differentially methylated region (DMR) upstream of H19 and a set of tissue-specific enhancers downstream of H19. The enhancers specifically activate Igf2 on the paternal chromosome and H19 on the maternal chromosome. The interactions between the enhancers and the genes are regulated by the DMR, which works as a selector by exerting dual functions: a methylated DMR on the paternal chromosome inactivates adjacent H19 and an unmethylated DMR on the maternal chromosome insulates Igf2 from the enhancers. These processes appear to involve methyl-CpG-binding proteins, histone deacetylases and the formation of chromatin insulator complexes. The Igf2/H19 region provides a unique model in which to study the roles of DNA methylation and chromatin structure in the regulation of chromosome domains.
Sasaki
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H
Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Yata, Mishima, Shizuoka 411-8540, Japan. hisasaki@lab.nig.ac.jp
Ishihara
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K
Kato
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R
D000818:Animals; D002843:Chromatin; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D051379:Mice; D008957:Models, Genetic; D009124:Muscle Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated
D002843:Chromatin; C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II