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| EPIGENETIC MECHANISMS UNDERLYING THE IMPRINTING OF THE MOUSE H19-GENE |
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| Author(s): BARTOLOMEI MS, WEBBER AL, BRUNKOW ME, TILGHMAN SM |
| Source: GENES & DEVELOPMENT Volume: 7 Issue: 9 Pages: 1663-1673 Published: SEP 1993 |
| Times Cited: 334 References: 45 |
| Abstract: The expression of the H19 gene is governed by parental imprinting in mammals. H19, an unusual gene encoding an RNA with no known function, is exclusively expressed from the maternal chromosome. In mouse, it lies 90 kb downstream from the Igf2 gene, which encodes a fetal-specific growth factor, insulin-like growth factor II, and is expressed primarily from the paternally inherited chromosome. In this report we have utilized interspecific hybrid mice to identify male-specific DNA methylation of a 7- to 9-kb domain surrounding the H19 gene and its promoter. This allele-specific methylation could function as a mark to suppress transcription of the H19 paternal allele. Consistent with this proposal, the H19 promoter displayed an open chromatin conformation only on the relatively unmethylated active maternal allele. In contrast, a cell type-specific enhancer that lies outside the methylation domain is hypersensitive to restriction enzyme digestion in nuclei on both maternal and paternal chromosomes. That the allele-specific methylation domain, coupled to the two H19 enhancers, contains all the information necessary for its imprinting was tested by examining two transgenic lines containing an internally deleted H19 transgene. Both displayed paternal-specific methylation of the transgene and maternal-specific expression. Although neither line has been tested in an inbred genetic background, and therefore the action of complex modifiers cannot be formally excluded, the result suggests that the sequences necessary for the imprinting of H19 have been identified. |
| Document Type: Article |
| Language: English |
Addresses:
1. PRINCETON UNIV, HOWARD HUGHES MED INST, PRINCETON, NJ 08544 USA
2. PRINCETON UNIV, DEPT MOLEC BIOL, PRINCETON, NJ 08544 USA |
| Publisher: COLD SPRING HARBOR LAB PRESS, 1 BUNGTOWN RD, PLAINVIEW, NY 11724 |
| Subject Category: Cell Biology; Developmental Biology; Genetics & Heredity |
| IDS Number: LW555 |
| ISSN: 0890-9369 |
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