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H19


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A gene that encodes one of the most abundant RNAs transcribed by the mouse embryo. The product of H19 is not a protein but an RNA particle with a sedimentation coefficient of 28S. H19 lies on chromosome 7, about 10 kb downstream from Igf2, the gene that encodes a protein called the insulin-like growth factor 2. The genes are oppositely imprinted, with H19 and Igf2 being expressed in the maternal and paternal homologs, respectively. Imprinting is controlled by the imprinting control region (ICR). The mechanism for parental imprinting of H19 and Igf2 is illustrated here. . Each embryonic cell has two homologs of chromosome 7, one maternally derived (M) and one paternally derived (P). ICR, lying between the two genes, contains binding sites (s1-s4) for the CTCF protein (q.v.). Methylation (CH3) of these sites prevents attachment of CTCF to the ICR. The enhancer (E) is free to loop over to the promoter of Igf2 and facilitate its transcription (II). When ICR is unmethylated (I), CTCF binds to it and insulates (i) Igf2 from E. So Igf2 is silenced, and H19 is switched on by its interaction with E. See Chronology, 2000, Bell and Felsenfeld; enhancers, insulator DNAs, insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), parental imprinting.

H19 Reprinted with permission from Nature (A. C. Bell and G. Felsenfeld, 2000, Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405: 482–485). © 2000 Macmillan Magazines Limited, London, UK.

Subjects: Genetics and Genomics.


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