BACKGROUND: Tax is the oncoprotein of HTLV-1 which deregulates signal 
transduction pathways, transcription of genes and cell cycle regulation of host 
cells. Transacting function of Tax is mainly mediated by its protein-protein 
interactions with host cellular factors. As to Tax-mediated regulation of gene 
expression of HTLV-1 and cellular genes, Tax was shown to regulate histone 
acetylation through its physical interaction with histone acetylases and 
deacetylases. However, functional interaction of Tax with histone 
methyltransferases (HMTase) has not been studied. Here we examined the ability 
of Tax to interact with a histone methyltransferase SUV39H1 that methylates 
histone H3 lysine 9 (H3K9) and represses transcription of genes, and studied the 
functional effects of the interaction on HTLV-1 gene expression.
RESULTS: Tax was shown to interact with SUV39H1 in vitro, and the interaction is 
largely dependent on the C-terminal half of SUV39H1 containing the SET domain. 
Tax does not affect the methyltransferase activity of SUV39H1 but tethers 
SUV39H1 to a Tax containing complex in the nuclei. In reporter gene assays, 
co-expression of SUV39H1 represses Tax transactivation of HTLV-1 LTR promoter 
activity, which was dependent on the methyltransferase activity of SUV39H1. 
Furthermore, SUV39H1 expression is induced along with Tax in JPX9 cells. 
Chromatin immunoprecipitation (ChIP) analysis shows localization of SUV39H1 on 
the LTR after Tax induction, but not in the absence of Tax induction, in JPX9 
transformants retaining HTLV-1-Luc plasmid. Immunoblotting shows higher levels 
of SUV39H1 expression in HTLV-1 transformed and latently infected cell lines.
CONCLUSION: Our study revealed for the first time the interaction between Tax 
and SUV39H1 and apparent tethering of SUV39H1 by Tax to the HTLV-1 LTR. It is 
speculated that Tax-mediated tethering of SUV39H1 to the LTR and induction of 
the repressive histone modification on the chromatin through H3 K9 methylation 
may be the basis for the dose-dependent repression of Tax transactivation of LTR 
by SUV39H1. Tax-induced SUV39H1 expression, Tax-SUV39H1 interaction and 
tethering to the LTR may provide a support for an idea that the above sequence 
of events may form a negative feedback loop that self-limits HTLV-1 viral gene 
expression in infected cells.