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Journal of Virology, October 2006, p. 10036-10044, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.00186-06

Coactivator-Associated Arginine Methyltransferase 1 Enhances Transcriptional Activity of the Human T-Cell Lymphotropic Virus Type 1 Long Terminal Repeat through Direct Interaction with Tax

Soo-Jin Jeong,{dagger} Hanxin Lu,{dagger} Won-Kyung Cho, Hyeon Ung Park, Cynthia Pise-Masison, and John N. Brady*

Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 41 Medlars Dr., Building 41, Room B302, Bethesda, Maryland 20892

Received 26 January 2006/ Accepted 17 July 2006

In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coimmunoprecipitation, and confocal microscopy experiments. Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).

* Corresponding author. Mailing address: Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 41 Medlars Dr., Building 41, Room B302, Bethesda, MD 20892. Phone: (301) 496-0986. Fax: (301) 496-4951. E-mail: bradyj{at}mail.nih.gov.

{dagger} S.-J.J. and H.L. contributed equally to this work.

Journal of Virology, October 2006, p. 10036-10044, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.00186-06




This article has been cited by other articles:

  • Dasgupta, A., Jung, K.-J., Jeong, S.-J., Brady, J. N. (2008). Inhibition of Methyltransferases Results in Induction of G2/M Checkpoint and Programmed Cell Death in Human T-Lymphotropic Virus Type 1-Transformed Cells. J. Virol. 82: 49-59 [Abstract] [Full Text]  


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