Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes

Abstract
Imprinting of the maternally-expressed Igf2r gene is controlled by an intronic imprint control element (ICE) known as Region2 that contains the promoter of the noncoding Air RNA, whose transcript overlaps the silenced paternal Igf2r promoter in an antisense orientation. Two novel imprinted genes, Slc22a2and Slc22a3 are described here that lie 110 and 155 kb 3′ toIgf2r and that are not overlapped by the Air transcript but are regulated by the Igf2r-ICE, as previously shown forIgf2r. These results identify a new cluster of imprinted genes whose repression by the bidirectional action of the Region2-ICE is independent of transcript overlap by the Air RNA.