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| ROLE FOR DNA METHYLATION IN GENOMIC IMPRINTING |
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| Author(s): LI E, BEARD C, JAENISCH R |
| Source: NATURE Volume: 366 Issue: 6453 Pages: 362-365 Published: NOV 25 1993 |
| Times Cited: 969 References: 21 |
| Abstract: THE paternal and maternal genomes are not equivalent and both are required for mammalian development1,2. The difference between the parental genomes is believed to be due to gamete-specific differential modification, a process known as genomic imprinting. The study of transgene methylation has shown that methylation patterns can be inherited in a parent-of-origin-specific manner3-7, suggesting that DNA methylation may play a role in 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 origin8-12. We have examined the expression of these three imprinted genes in mutant mice that are deficient in DNA methyltransferase activity13. We report here that expression of all three genes was affected in mutant embryos: the normally silent paternal allele of the H19 gene was activated, whereas the normally active paternal allele of die Igf-2 gene and the active maternal allele of the Igf-2r gene were repressed. Our results demonstrate that a normal level of DNA methylation is required for controlling differential expression of the paternal and maternal alleles of imprinted genes. |
| Document Type: Article |
| Language: English |
Addresses:
1. MIT, WHITEHEAD INST BIOMED RES, 9 CAMBRIDGE CTR, CAMBRIDGE, MA 02142 USA
2. MIT, DEPT BIOL, CAMBRIDGE, MA 02142 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: MJ705 |
| ISSN: 0028-0836 |
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