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Research ArticleArticle

Histone Deacetylase Inhibitors Increase Human Arylamine N-Acetyltransferase-1 Expression in Human Tumor Cells

Scott Paterson, Kok L. Sin, Jacky M. Tiang, Rodney F. Minchin and Neville J. Butcher
Drug Metabolism and Disposition January 2011, 39 (1) 77-82; DOI: https://doi.org/10.1124/dmd.110.036202
Scott Paterson
School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
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Kok L. Sin
School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
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Jacky M. Tiang
School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
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Rodney F. Minchin
School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
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Neville J. Butcher
School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
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Abstract

Arylamine N-acetyltransferase-1 (NAT1) has been associated with disorders involving folate metabolism, such as spina bifida, as well as numerous human cancers. As a result, the transcriptional and post-transcriptional regulation of NAT1 activity has been extensively studied. However, little work has been reported on the epigenetic control of NAT1 expression. Here, we demonstrate that the histone deacetylase inhibitor trichostatin A (TSA) increases NAT1 activity in human cancer cells by increasing transcription from the proximal promoter NATb. A specific Sp1 binding site was identified as essential for optimal induction of NAT1 by TSA. However, TSA did not increase the expression of Sp1 in HeLa cells. Instead, TSA increased the acetylation of histones associated with the NATb promoter. This allowed recruitment of Sp1 to the promoter along with acetylated histones. We propose that NAT1 transcription is partially repressed by the local chromatin condensation in the vicinity of NATb and that histone deacetylase inhibition leads to up-regulation of NAT1 expression via a direct change in chromatin conformation.

Footnotes

    • Received September 2, 2010.
    • Accepted September 23, 2010.
  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.110.036202.

  • ABBREVIATIONS:

    NAT1
    arylamine N-acetyltransferase-1
    bp
    base pairs
    TSA
    trichostatin A
    HDAC
    histone deacetylase
    DMSO
    dimethyl sulfoxide
    PBS
    phosphate-buffered saline
    PCR
    polymerase chain reaction
    qPCR
    quantitative real-time polymerase chain reaction
    DTT
    dithiothreitol
    PMSF
    phenylmethylsulfonyl fluoride
    EMSA
    electromobility shift assay
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    ChiP
    chromatin immunoprecipitation.

  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 39 (1)
Drug Metabolism and Disposition
Vol. 39, Issue 1
1 Jan 2011
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Research ArticleArticle

Histone Deacetylase Inhibitors Increase Human Arylamine N-Acetyltransferase-1 Expression in Human Tumor Cells

Scott Paterson, Kok L. Sin, Jacky M. Tiang, Rodney F. Minchin and Neville J. Butcher
Drug Metabolism and Disposition January 1, 2011, 39 (1) 77-82; DOI: https://doi.org/10.1124/dmd.110.036202

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Research ArticleArticle

Histone Deacetylase Inhibitors Increase Human Arylamine N-Acetyltransferase-1 Expression in Human Tumor Cells

Scott Paterson, Kok L. Sin, Jacky M. Tiang, Rodney F. Minchin and Neville J. Butcher
Drug Metabolism and Disposition January 1, 2011, 39 (1) 77-82; DOI: https://doi.org/10.1124/dmd.110.036202
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