Delta-like and Gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12

The distal portion of mouse chromosome 12 is imprinted. to date, however, G tl2 is the only imprinted gene identified on chromosome 12. Gtl2 encodes mu ltiple alternatively spliced transcripts with no apparent open reading fram e. Using conceptuses with maternal or paternal uniparental disomy for chrom osome 12 (UPD12), we found that Gtl2 is expressed from the maternal allele and methylated at the 5' end of the silent paternal allele, A reciprocally imprinted gene, Delta-like (Dlk), with homology to genes involved in the No tch signalling pathway was identified 80 kb upstream of Gtl2, Dlk was expre ssed exclusively from the paternal allele in both the embryo and placenta, but the CpG-island promoter of Dlk was completely unmethylated on both pare ntal alleles, Rather, a paternally methylated region was identified in the last exon of the active Dlk allele. The proximity, reciprocal imprinting an d methylation in this domain are reminiscent of the co-ordinately regulated Igf2-H19 imprinted domain on mouse chromosome 7, Like H19 and Igf2, Gtl2 a nd Dlk were found to be co-expressed in the same tissues throughout develop ment, though not after birth. These results have implications for the regul ation, function and evolution of imprinted domains.