Role for DNA methylation in genomic imprinting (original) (raw)

Nature volume 366, pages 362–365 (1993)Cite this article

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 lgf-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 HI9 gene was activated, whereas the normally active paternal allele of the 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.

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Author notes

  1. En Li
    Present address: Cardiovascular Research Center, Massachusetts General Hospital-East, 149 13th Street, Charlestown, Massachusetts, 02129, USA

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts, 02142, USA
    En Li, Caroline Beard & Rudolf Jaenisch

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  1. En Li
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  2. Caroline Beard
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  3. Rudolf Jaenisch
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Li, E., Beard, C. & Jaenisch, R. Role for DNA methylation in genomic imprinting.Nature 366, 362–365 (1993). https://doi.org/10.1038/366362a0

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