ABSTRACT
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).