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H19  and  Igf2  are expressed in a monoallelic fashion from the maternal and paternal chromosomes, respectively. A region upstream of  H19  has been shown to regulate such imprinted expression of both genes in  cis . We have taken advantage of a loxP /cre recombinase-based strategy to delete this region in mice in a conditional manner to determine the temporal requirement of the upstream region in initiating and maintaining the imprinted expression of  H19  and  Igf2 . Analysis of allele-specific expression of  H19  and  Igf2  and DNA methylation at the  H19  promoter demonstrates that this region controls the monoallelic expression of the two genes in different ways, suggesting that it harbors two functionally distinct regulatory elements. Continued presence of the region is required to silence maternal  Igf2  in accordance with its proposed role as an insulator. However, it does not have a direct role in keeping the paternal  H19  promoter silenced. Instead, on the paternal chromosome, the upstream element mediates epigenetic modifications of the  H19  promoter region during development, leading to transcriptional silencing of  H19 . Thereafter, its presence is redundant for preventing transcription. Presently, this temporal requirement of the silencing element appears to be a unique  cis activity in the mammalian system. However, it is likely that other cis -acting elements, positive and negative, have the ability to effect stable changes in the chromatin structure and are not constantly required to give signals to the transcriptional machinery.

genes and development

H19 and Igf2 monoallelic expression is regulated in two distinct ways by a shared cis acting regulatory region upstream of H19