Conserved proximal promoter elements control repulsive guidance molecule c/hemojuvelin (Hfe2) gene transcription in skeletal muscle

Christopher J. Severyn, Peter Rotwein

    Research output: Contribution to journalArticlepeer-review

    5 Scopus citations

    Abstract

    Repulsive guidance molecule c (RGMc; gene symbol: Hfe2) plays a critical role in iron metabolism. Inactivating mutations cause juvenile hemochromatosis, a severe iron overload disorder. Understanding mechanisms controlling RGMc biosynthesis has been hampered by minimal information about the RGMc gene. Here we define the structure, examine the evolution, and establish mechanisms of regulation of the mouse RGMc gene. RGMc is a 4-exon gene that undergoes alternative RNA splicing to yield 3 mRNAs with 5' different untranslated regions. Gene transcription is induced during myoblast differentiation, producing all 3 mRNAs. We identify 3 critical promoter elements responsible for transcriptional activation in skeletal muscle, comprising paired E-boxes, a putative Stat and/or Ets element, and a MEF2 site, and muscle transcription factors myogenin and MEF2C stimulate RGMc promoter function in non-muscle cells. As these elements are conserved in RGMc genes from multiple species, our results suggest that RGMc has been a muscle-enriched gene throughout its evolutionary history.

    Original languageEnglish (US)
    Pages (from-to)342-351
    Number of pages10
    JournalGenomics
    Volume96
    Issue number6
    DOIs
    StatePublished - Dec 2010

    Keywords

    • Hemojuvelin
    • Juvenile hemochromatosis
    • Molecular evolution
    • RGMc
    • Repulsive guidance molecule (RGM)
    • Transcriptional regulation

    ASJC Scopus subject areas

    • Genetics

    Fingerprint Dive into the research topics of 'Conserved proximal promoter elements control repulsive guidance molecule c/hemojuvelin (Hfe2) gene transcription in skeletal muscle'. Together they form a unique fingerprint.

    Cite this