COORDINATE REGULATION OF IGF-2 AND H19 IN CULTURED-CELLS

The insulin-like growth factor 2 (Igf-2) acid H19 genes are physically linked on mouse distal chromosome 7 and are reciprocally imprinted. W e investigated the molecular basis of the parental imprints in somatic cell cultures derived from normal embryos or from their littermates w ith maternal uniparental disomy for distal chromosome 7 (Matdi7). In n ormal cells, the two genes appeared to respond to similar regulatory f actor(s), since both genes were coordinately up-regulated upon growth arrest and cell clones which had lost expression of one gene had lost expression of the other. However, in a clone of MatDi7 cells (MatDi7 1 -1a), which spontaneously began to express the maternally derived copy of Igf-2, Igf-2 and H19 were not coordinately regulated. MatDi7 1-1a cells showed de novoes upstream of Igf-2 and also within the H19 promo ter, epigenetic modifications normally seen only on the paternal chrom osome. The data provide new experimental evidence for previously hypot hesized mechanisms suggesting that Igf-2 and H19 are coordinately regu lated.