BACKGROUND: The rate of transcription of the HIV-1 viral genome is mediated by 
the interaction of the viral protein Tat with the LTR and other transcriptional 
machinery. These specific interactions can be affected by the state of 
post-translational modifications on Tat. Previously, we have shown that Tat can 
be phosphorylated and acetylated in vivo resulting in an increase in the rate of 
transcription. In the present study, we investigated whether Tat could be 
methylated on lysine residues, specifically on lysine 50 and 51, and whether 
this modification resulted in a decrease of viral transcription from the LTR.
RESULTS: We analyzed the association of Tat with histone methyltransferases of 
the SUV39-family of SET domain containing proteins in vitro. Tat was found to 
associate with both SETDB1 and SETDB2, two enzymes which exhibit 
methyltransferase activity. siRNA against SETDB1 transfected into cell systems 
with both transient and integrated LTR reporter genes resulted in an increase in 
transcription of the HIV-LTR in the presence of suboptimal levels of Tat. In 
vitro methylation assays with Tat peptides containing point mutations at lysines 
50 and 51 showed an increased incorporation of methyl groups on lysine 51, 
however, both residues indicated susceptibility for methylation.
CONCLUSION: The association of Tat with histone methyltransferases and the 
ability for Tat to be methylated suggests an interesting mechanism of 
transcriptional regulation through the recruitment of chromatin remodeling 
proteins to the HIV-1 promoter.