GENOMIC IMPRINTING IN MICE - ITS FUNCTION AND MECHANISM

Genomic imprinting is an epigenetic phenomenon by which the two parent al alleles of a gene are differentially expressed. Although the functi on of genomic imprinting is not clear, it has been proposed that it ev olved in mammals to regulate intrauterine growth. This proposal is con sistent with experiments that were designed to reveal the mechanism an d impact of genomic imprinting in a region of mouse chromosome 7 that contains four imprinted genes: Mash-2 (a transcription factor) and H19 (a noncoding RNA) are maternally expressed, whereas Insulin-2 (Ins-2) and Insulin-like growth factor 2 (Igf-2) are paternally expressed. Tw o targeted disruptions at the locus were generated in mice; these supp ort the hypothesis that the function of the H19 gene is to set up the imprinting of both Igf-2 and Ins-2. H19-transcription on the maternal chromosome precludes transcription of the other two genes by a mechani sm that involves competition for a common set of enhancers. On the pat ernal chromosome the H19 gene is silenced by DNA methylation, thus per mitting the use of enhancers by the other genes.