Coordinate regulation of Igf-2 and H19 in cultured cells.
The insulin-like growth factor 2 (Igf-2) and H19 genes are physically linked on mouse distal chromosome 7 and are reciprocally imprinted. We investigated the molecular basis of the parental imprints in somatic cell cultures derived from normal embryos or from their littermates with maternal uniparental disomy for distal chromosome 7 (MatDi7). In normal cells, the two genes appeared to respond to similar regulatory factor(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 novo methylation of sites upstream of Igf-2 and also within the H19 promoter, epigenetic modifications normally seen only on the paternal chromosome. The data provide new experimental evidence for previously hypothesized mechanisms suggesting that Igf-2 and H19 are coordinately regulated.
Eversole-Cire
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Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, University of Southern California, School of Medicine, Los Angeles 90033, USA.
Ferguson-Smith
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AC
Surani
M A
MA
Jones
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PA
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D015254:DNA Modification Methylases / Q000378:metabolism*; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000032:analysis; D022661:RNA, Untranslated; D015183:Restriction Mapping; D013997:Time Factors
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D015254:DNA Modification Methylases