Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians

Guillaume Smits, Andrew J. Mungall, Sam Griffiths-Jones, Paul Smith, Delphine Beury, Lucy Matthews, Jane Rogers, Andrew J. Pask, Geoff Shaw, John L. VandeBerg, John R. McCarrey, Marilyn B. Renfree, Wolf Reik, Ian Dunham

    Research output: Contribution to journalArticle

    130 Scopus citations

    Abstract

    Comparisons between eutherians and marsupials suggest limited conservation of the molecular mechanisms that control genomic imprinting in mammals. We have studied the evolution of the imprinted IGF2-H19 locus in therians. Although marsupial orthologs of protein-coding exons were easily identified, the use of evolutionarily conserved regions and low-stringency Bl2seq comparisons was required to delineate a candidate H19 noncoding RNA sequence. The therian H19 orthologs show miR-675 and exon structure conservation, suggesting functional selection on both features. Transcription start site sequences and poly(A) signals are also conserved. As in eutherians, marsupial H19 is maternally expressed and paternal methylation upstream of the gene originates in the male germline, encompasses a CTCF insulator, and spreads somatically into the H19 gene. The conservation in all therians of the mechanism controlling imprinting of the IGF2-H19 locus suggests a sequential model of imprinting evolution.

    Original languageEnglish (US)
    Pages (from-to)971-976
    Number of pages6
    JournalNature Genetics
    Volume40
    Issue number8
    DOIs
    StatePublished - Aug 1 2008

    ASJC Scopus subject areas

    • Genetics

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    Smits, G., Mungall, A. J., Griffiths-Jones, S., Smith, P., Beury, D., Matthews, L., Rogers, J., Pask, A. J., Shaw, G., VandeBerg, J. L., McCarrey, J. R., Renfree, M. B., Reik, W., & Dunham, I. (2008). Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians. Nature Genetics, 40(8), 971-976. https://doi.org/10.1038/ng.168