Mechanisms regulating imprinted genes in clusters.

Clustered imprinted genes are regulated by differentially methylated imprinting control regions (ICRs) that affect gene activity and repression in cis over a large region. Although a primary imprint signal for each of these clusters is DNA methylation, different mechanisms are used to establish and maintain these marks. The majority of ICRs are methylated in the maternal germline and are usually promoters for antisense transcripts whose elongation is associated with imprinting control in the domain. In contrast, ICRs methylated in the paternal germline do not appear to act as promoters and are located between genes. At least one, at the Igf2/H19 locus, is known to function as an insulator. Analysis of ICRs suggests that maternal and paternal methylation imprints function in distinct ways.