Epigenetic regulation is a determinant of the cell line specific expression of the UDP glycosyltransferase 3A1 and 3A1 genes

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    Abstract

    The UDP glycosyltransferases (UGTs) are a super-family of
    enzymes involved in the metabolism of xenobiotics and endogenous
    molecules. Variations in UGT expression have been associated
    with disease states and inter-individual variation in response
    to drug therapy. The UGT3A family was discovered and characterised
    by our laboratory. Upon investigating UGT3A expression
    in a range of cell lines, we found a large number in which
    UGT3A1 was not expressed. To determine if epigenetic mechanisms
    are responsible for this lack of expression, cell lines were
    treated with the demethylating agent 5-aza-20-deoxycytidine (5-
    aza-dC), and the histone deacetylase inhibitor trichostatin A
    (TSA), and levels of UGT3A mRNA measured. In three cell lines
    (T47D, MCF-7 and ZR75.1), 5-aza-dC induced UGT3A1 expression
    from 8.9-fold (ZR75.1, p = 0.024) up to 12.2-fold (T47D,
    p = 0.007). TSA alone did not induce UGT3A1 expression, but
    in some cases, was synergistic with 5-aza-dC. Neither chemical
    had an effect on UGT3A2 expression in these three cell lines. In
    MDA-MB-453 cells, only 5-aza-dC with TSA induced UGT3A1
    expression (14.5-fold, p = 0.036), while UGT3A2 was induced by
    5-aza-dC (27.8-fold, p = 0.002), and 5-aza-dC with TSA (23.9-
    fold, p = 0.012). Thus our preliminary data indicates that epigenetic
    mechanisms, particularly DNA methylation, are a determinant
    of cell line specific expression of UGT3A1 and UGT3A2.
    Bisulfite sequence analysis will be performed to identify the methylation
    status of predicted promoter CpG islands. This should
    provide further novel insights into the epigenetic regulation of
    the UGT3A family.
    Original languageEnglish
    Pages (from-to)58
    JournalThe FEBS Journal
    Volume282
    Issue numberS1
    DOIs
    Publication statusPublished - 2015
    Event40th FEBS Conference – The Biochemical Basis of Life - Estrel Convention Center, Berlin, Germany
    Duration: 4 Jul 20159 Jul 2015

    Keywords

    • epigenetic regulation
    • enzymes
    • glycosyltransferase

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