Identification of the Principal Imprinting Control Region at the Gnas Cluster- a new Nature
Christine M. Williamson, Martin D. Turner, Simon T. Ball, Wade T. Nottingham, Peter Glenister, Martin Fray, Antonius Plagge, Nicola Powles-Glover, Gavin Kelsey, Mark Maconochie & Jo Peters
Genomic imprinting was recognised twenty or so years ago, and has since excited intense interest. Genomic imprinting results in the silencing of genes according to parental origin such that the two alleles function differently. There are relatively few imprinted genes (only eighty or so have been identified) but many have roles in growth, both before and after birth, in obesity, in behaviour and in cancer. Imprinted genes tend to occur in clusters. There is growing evidence that there is a single region of DNA, called an Imprinting Control Region (ICR), within each cluster that regulates expression of the imprinted genes. An ICR is a region of DNA that is differentially methylated in sperm and egg. It can act over hundreds of kilobases to control gene expression. We have been investigating control of imprinting in a relatively small, but complex, cluster of imprinted genes around the Gnas locus that, in mice and humans, is well conserved in its organisation. We had previously shown that an ICR controls the tissue–specific silencing of a paternally derived copy of a single gene within the complex. In our newly published paper we have identified a second ICR that is the principal ICR for the whole Gnas cluster and acts on the previously identified ICR. The Gnas cluster is truly exceptional in containing two such imprinting control regions. Our results indicate that an intricate system of regulatory interactions may be required for imprinted gene expression.