The detailed entries of the Imprinted Gene Catalogue database were created by Benjamin Tycko, Columbia University, New York and are updated by Ian Morison


 

Detailed entry for Gene:

H19

Chromosome:

Human Chr11p15.5
Mouse Chr7 (distal)

Links:

OMIM  MethDB (mouse)

Imprinting:

The paternal allele of H19 is silenced; maternal allele active in a wide array of mesenchymal and epithelial tissues, both in mice and humans (Bartolomei MS et al, 1991; Zhang Y et al, 1993; Zhang Y et al, 1992). H19 and Igf2 are inversely regulated in cis through shared insulator and enhancer sequences (Bell AC et al, 2000; Hark AT et al, 2000; Leighton PA et al, 1995). Accordingly, net expression of H19 generally parallels that of Igf2 (Drewell RA et al, 2000; Leighton PA et al, 1995; Ohlsson R et al, 1994; Pachnis V et al, 1988).

Gene Product:

H19 encodes an abundant spliced and polyadenylated RNA that has a conserved exon-intron structure among mammals, but that lacks conserved open reading frames. H19 RNA accumulates in the cytoplasm (Brannan CI et al, 1990; Li YM et al, 1998).

Functional Data:

Somatic overgrowth was observed in knockout mice lacking the H19 gene and upstream sequences (Leighton PA et al, 1995). Igf2 showed loss of imprinting in these mice and crossing of H19-minus females with Igf2-minus males abrogated the overgrowth of the conceptuses (Leighton PA et al, 1995). This suggested that the biological function of H19 may be restricted to controlling Igf2 in cis. However, in another study, deletion of a smaller sequence element upstream of H19 led to activation of the paternal H19 allele, and these mice were growth-retarded, without a measurable effect on Igf2 expression (Drewell RA et al, 2000). Expression of H19 RNA inhibited soft agar growth and tumorigenicity in some, but not all, transfected cancer cells (Hao Y et al, 1993; Isfort RJ et al, 1997). The H19 gene is silenced, either by de novo DNA hypermethylation of the maternal allele and immediate upstream DNA, or by physical loss of this allele, in most Wilms' tumors and in hepatoblastomas, adrenal cortical carcinomas and embryonal rhabdomyosarcomas (Moulton T et al, 1994; Steenman MJ et al, 1994; Taniguchi T et al, 1995; Casola S et al, 1997; Fukuzawa R et al, 1999; Liu J et al, 1995). De novo methylation of H19, associated with relaxation of IGF2 imprinting, is also observed in a subset of cases of classical Beckwith-Wiedemann syndrome (Catchpoole D et al, 1997), and in a BWS-like overgrowth disorder associated with predisposition to Wilms' tumour (Morison IM et al, 1996).

 

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