Trends in Genetics
OutlookGenomic imprinting in mammals: an interplay between chromatin and DNA methylation?
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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