Imprinting mechanisms in mammals.

Imprinting is a genetic mechanism that determines expression or repression of genes according to their parental origin. Some imprinted genes occur in clusters in the genome. Recent work using transgenic mice shows that multiple cis-acting sequences are needed for correct imprinting. Mutation analysis in a normal chromosomal context reveals the importance of imprinting centres for regional establishment or maintenance of imprinting in a cluster. Elements that contribute to the function of imprinting centres and regional propagation of the imprints are CpG-rich differentially methylated regions (that during development retain germline imposed methylation or demethylation), direct repeat clusters, and unusual RNAs (antisense, non-translated etc.). The interaction of these cis elements with transacting factors such as methylase and chromatin factors establishes a hierarchical control system with local and regional effects.