Abstract
The mouse insulin-like growth factor 2 (
Igf2
) locus is a complex genomic region that produces multiple transcripts from alternative promoters. Expression at this locus is regulated by parental imprinting. However, despite the existence of putative imprinting control elements in the
Igf2
upstream region, imprinted transcriptional repression is abolished by null mutations at the linked
H19
locus. To clarify the extent to which the
Igf2
upstream region contains autonomous imprinting control elements we have performed functional and comparative analyses of the region in the mouse and human. Here we report the existence of multiple, overlapping imprinted (maternally repressed) sense and antisense transcripts that are associated with a tandem repeat in the mouse
Igf2
upstream region. Regions flanking the repeat exhibit tissue-specific parental allelic methylation patterns, suggesting the existence of tissue-specific control elements in the upstream region. Studies in
H19
null mice indicate that both parental allelic methylation and monoallelic expression of the upstream transcripts depends on an intact
H19
gene acting in cis. The homologous region in human
IGF2
is structurally conserved, with the significant exception that it does not contain a tandem repeat. Our results support the proposal that tandem repeats act to target methylation to imprinted genetic loci.