The early expressed HIV-1 genes regulate DNMT1 expression.

DNA methylation-mediated transcriptional regulation is essential for human development and diverse diseases ensue when this process is dysregulated. Viruses, including HIV-1, alter the expression of human DNA methyltransferases (DNMTs) and various T cell-specific genes. Here we show that HIV-1 induction of DNMT1 results from overexpression of the early expressed HIV-1 proteins, and this induction is prevented with resveratrol which interferes with the transcription factor AP1 pathway. The HIV-1 responsive element resides in the 5' most 420 bp of the -1634 to +71 DNMT1 promoter; positioning of this truncated promoter proximal to a hybrid SV40-DNMT1 reporter results in HIV-1-dependent regulation. HIV-1 mediated induction of DNMT1 is not specific to T-cells, and does not require receptor-mediated endocytosis. The characterization of HIV-1 mediated DNMT1 regulation provides a basis for identifying viral and cellular factors necessary for the de novo DNA methylation of cellular genes.