Mechanisms of Igf2/H19 Imprinting: DNA Methylation, Chromatin and Long-Distance Gene Regulation

抄録

The mouse Igf 2 and H 19 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 H 19 and a set of tissuespecific enhancers downstream of H 19. The enhancers specifically activate Igf 2 on the paternal chromosome and H 19 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 H 19 and an unmethylated DMR on the maternal chromosome insulates Igf 2 from the enhancers. These processes appear to involve methyl-CpG-binding proteins, histone deacetylases and the formation of chromatin insulator complexes. The Igf 2/H 19 region provides a unique model in which to study the roles of DNA methylation and chromatin structure in the regulation of chromosome domains.