FEBS Letters
Volume 583, Issue 12 , Pages 1880-1886, 18 June 2009

The histone methyltransferase, NSD2, enhances androgen receptor-mediated transcription

Edited by Ivan Sadowski

  • Hee-Bum Kang

      Affiliations

    • Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
    • Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
    • These authors contributed equally to this work.
    • ,
  • Youngsok Choi

      Affiliations

    • Fertility Center of CHA General Hospital, CHA Research Institute, Pochon CHA University, Seoul 135-081, South Korea
    • These authors contributed equally to this work.
    • ,
  • Jae Myun Lee

      Affiliations

    • Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
    • Department of Microbiology, Yonsei University College of Medicine, South Korea
    • ,
  • Kyung-Chul Choi

      Affiliations

    • Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
    • Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
    • ,
  • Han-Cheon Kim

      Affiliations

    • Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
    • Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
    • ,
  • Jung-Yoon Yoo

      Affiliations

    • Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
    • Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
    • ,
  • Yoo-Hyun Lee

      Affiliations

    • Department of Food and Nutrition, The University of Suwon, South Korea
    • ,
  • Ho-Geun Yoon

      Affiliations

    • Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
    • Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
    • Corresponding Author InformationCorresponding author. Address: Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea. Fax: +82 2 312 5041.

Received 31 January 2009; received in revised form 18 April 2009; accepted 22 May 2009. published online 28 May 2009.

Abstract 

In this study, we discovered that NSD2 specifically interacts with the DNA-binding domain of androgen receptor (AR) via its HMG domain, and the nuclear translocation of both NSD2 and AR is enhanced in the presence of ligand. Furthermore, we also demonstrated that the over expression of NSD2, but not of NSD2 (ΔSET) HMT-activity defective mutant, enhanced the mRNA level of PSA in a dose-dependent manner. A chromatin immunoprecipitation assay showed that NSD2 protein is recruited to the enhancer region of the PSA gene by AR in an agonist-enhanced manner. Taken together, these results uncover a potential role for NSD2 in AR-mediated transcription, implicating NSD2 in prostate carcinogenesis.

Structured summary

MINT-7103766: NSD2 (uniprotkb:O96028) physically interacts (MI:0914) with alpha AR (uniprotkb:P10275) by anti tag coimmunoprecipitation (MI:0007)

MINT-7103748: NSD2 (uniprotkb:O96028) physically interacts (MI:0915) with alpha AR (uniprotkb:P10275) by two hybrid (MI:0018)

MINT-7103800, MINT-7103819: alpha AR (uniprotkb:P10275) binds (MI:0407) to NSD2 (uniprotkb:O96028) by pull down (MI:0096)

MINT-7103785: NSD2 (uniprotkb:O96028) colocalizes (MI:0403) with alpha AR (uniprotkb:P10275) by fluorescence microscopy (MI:0416)

MINT-7103733: P53 (uniprotkb:P04637) physically interacts (MI:0915) with alpha AR (uniprotkb:P10275) by two hybrid (MI:0018)

Abbreviations: NSD2, nuclear SET domain-containing 2, AR, androgen receptor, HMT, histone methyltransferase, ChIP, chromatin immunoprecipitation

Keywords: Nuclear SET domain-containing 2, Androgen receptor, Histone methyltransferase, Prostate cancer, Transcription

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PII: S0014-5793(09)00413-X

doi:10.1016/j.febslet.2009.05.038

FEBS Letters
Volume 583, Issue 12 , Pages 1880-1886, 18 June 2009

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