Trends in Genetics
Volume 15, Issue 11, 1 November 1999, Pages 431-435
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Genomic imprinting in mammals: an interplay between chromatin and DNA methylation?

https://doi.org/10.1016/S0168-9525(99)01822-3Get rights and content

Abstract

Most imprinted loci have key regulatory elements that are methylated on only one of the parental chromosomes. For several of these ‘differentially methylated regions’, recent studies establish that the unmethylated chromosome has a specialized chromatin organization that is characterized by nuclease hypersensitivity. The novel data raise the question of whether specific proteins and associated chromatin features regulate the allele-specificity of DNA methylation at these imprinting control elements.

Section snippets

Differentially methylated regions

More recently, homologous-recombination experiments in the mouse have demonstrated that individual DMRs are, indeed, important for the expression of imprinted genes. For example, a DMR located upstream of the mouse H19 gene7 that is methylated on the paternal chromosome (Fig. 1) was shown to be essential for the imprinted expression both of H19 and of the neighbouring, paternally expressed gene that encodes insulin-like growth factor-2 (Igf2)8. In particular, the deletion of this DMR on the

Interplay between chromatin and DNA methylation

In three in vivo chromatin studies15, 16, 17, nuclease-hypersensitive sites were detected in the DMR upstream of the mouse H19 gene. Five DNase-I-hypersensitive sites (and hypersensitivity to different restriction endonucleases) were detected on the unmethylated maternal chromosome, but not on the methylated paternal chromosome (Fig. 1). These hypersensitive sites were apparent in all embryonic and adult material analyzed, and also in tissues that do not express the H19 (and the neighbouring

Perspectives

It is notable that, similar to the differential DNA methylation, the parental chromosome-specific nuclease hypersensitivity in the H19, U2af1-rs1 and SNRPN genes is present in all tissues analysed. This suggests that at least some of the associated factors are constitutive and could be involved in preventing the DMR from becoming methylated during development. Such a role would be most pertinent during pre-gastrulation stages, when the global wave of de novo methylation occurs6. Significantly,

Acknowledgements

We thank W. Reik and G. Kelsey for helpful comments and discussion. Supported by grants from the Human Frontier Science Program, the Ministry of Agriculture, Fisheries and Food (to R. Feil and W. Reik), and the Babraham Institute (R. Feil is a Babraham Research Fellow).

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