The Dlk1 and Gtl2 genes are linked and reciprocally imprinted

Genes subject to genomic imprinting exist in large chromosomal domains, pro bably reflecting coordinate regulation of the genes within a cluster. Such regulation has been demonstrated for the H19, Igf2, and Ins2 genes that sha re a bifunctional imprinting control region. We have identified the Dlk1 ge ne as a new imprinted gene that is paternally expressed. Furthermore, we sh ow that Dlk1 is tightly linked to the maternally expressed Gtl2 gene. Dlk1 and Grl2 are coexpressed and respond in a reciprocal manner to loss of DNA methylation. These genes are likely to represent a new example of coordinat ed imprinting of linked genes.