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.
Youngblood
Ben
B
Program in Biomolecular Science and Engineering, University of California, Santa Barbara, California 93106-9510, USA.
Reich
Norbert O
NO
D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D005814:Genes, Viral / Q000235:genetics*; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection
C411744:DMAP1 protein, human; D018076:DNA, Complementary; D054298:Human Immunodeficiency Virus Proteins; D012097:Repressor Proteins; D018808:Transcription Factor AP-1