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Intronic promoters and their noncoding transcripts: A new source of cancer-associated genes

Authors

  • Manfred Relle,

    Corresponding author
    1. I. Department of Medicine, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany
    • I. Department of Medicine, Division of Rheumatology and Clinical Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany.

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  • Marc Becker,

    1. I. Department of Medicine, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany
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  • Ralf G. Meyer,

    1. Department of Hematology, Oncology, and Pneumology, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany
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  • Michael Stassen,

    1. Institute for Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany
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  • Andreas Schwarting

    Corresponding author
    1. I. Department of Medicine, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany
    • I. Department of Medicine, Division of Rheumatology and Clinical Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany.

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  • This article was published online on 28 August 2012. An error was subsequently identified by the author in the legend of Figure (B). The word “ZP3 repeat” [17] should be “ZP3 repeat” [26]. This has now been corrected on 19 September 2012. The authors regret this error.

Abstract

Recent studies of mammalian genomes suggest that alternative promoters are associated with various disorders, including cancer. Here we present an intronic promoter of the murine proteinase 3 gene, which drives the expression of an alternative mRNA in intron 2 of the prtn3 gene. The proximal promoter sequences were identified and a series of promoter deletion constructs were used to identify the sequence elements that are required for basal promoter activity. Expression of the homeobox transcription factor CUX1 p75 isoform was found to suppress the activity of the alternative PR3 promoter. Data base analyses, multiple alignments and expression data showed that the intronic PR3 promoter is active in leukemia and other tumor cells as well as in mouse embryo, male mammary gland and bone marrow. In the spleen, the transcript is exclusively expressed by Gr-1int/CD11b+ cells, which are also known as myeloid-derived suppressor cells (MDSCs). In humans, an alternative transcript of the PR3-gene could be detected in the bone marrow and in various cancer cell lines but not in primary leukemia cells, suggesting a species-overarching function of this kind of promoter. Therefore, the alternative PR3 promoter and its mRNA may be useful tools to investigate the fate of hematopoietic stem cells. © 2012 Wiley Periodicals, Inc.

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