Retroviral mediated expression of the human myeloid nuclear antigen in a null cell line upregulates Dlk1 expression

Kevin L. Doggett, Judith A. Briggs, MacRae F. Linton, Sergio Fazio, David R. Head, Jingping Xie, Yuko Hashimoto, Jorge Laborda, Robert C. Briggs

    Research output: Contribution to journalArticle

    11 Scopus citations

    Abstract

    The human myeloid nuclear differentiation antigen (MNDA) is a hematopoietic cell specific nuclear protein. MNDA and other related gene products interact with and alter the activity of a large number of proteins involved in regulating specific gene transcription. MNDA and related genes exhibit expression characteristics, which suggest functions unique to specific lineages of cells, in addition to mediating the effects of interferons. Cells of the human K562 myeloid line do not express MNDA and are relatively immature compared to lines that express MNDA (HL-60, U937, and THP1). The hypothesis that MNDA influences the expression of specific genes was tested by creating MNDA expressing K562 cells using stable retroviral mediated gene transfer followed by evaluation of transcription profiles. Two macroarrays containing a total of 2,350 cDNAs of known genes showed a specific up-regulation of Dlk1 expression in MNDA expressing K562 cell clones. Real time quantitative RT-PCR analysis confirmed an average of over 3- and 7-fold upregulation of Dlk1 in two clones of MNDA expressing K562 cells. The effects on Dlk1 were also confirmed by Northern blotting. Dlk1 is essential for normal hematopoiesis and abnormal expression is a proposed marker of myelodysplastic syndrome. Additional screening of transcription profiles after induced erythroid and megakaryoblastic differentiation showed no additional gene transcripts altered by the presence of MNDA. These results indicate that MNDA alters expression of a gene essential for normal hematopoiesis.

    Original languageEnglish (US)
    Pages (from-to)56-66
    Number of pages11
    JournalJournal of cellular biochemistry
    Volume86
    Issue number1
    DOIs
    StatePublished - Jan 1 2002

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    Keywords

    • Dlk1 expression
    • Hematopoiesis
    • K562
    • MNDA
    • Myelodysplastic syndrome
    • Transcription profiles

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    Doggett, K. L., Briggs, J. A., Linton, M. F., Fazio, S., Head, D. R., Xie, J., Hashimoto, Y., Laborda, J., & Briggs, R. C. (2002). Retroviral mediated expression of the human myeloid nuclear antigen in a null cell line upregulates Dlk1 expression. Journal of cellular biochemistry, 86(1), 56-66. https://doi.org/10.1002/jcb.10190