Tax relieves transcriptional repression by promoting histone deacetylase 1 release from the human T-cell leukemia virus type 1 long terminal repeat.
Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by the viral transcriptional activator Tax. Tax activates viral transcription through interaction with the cellular transcription factor CREB and the coactivators CBP/p300. In this study, we have analyzed the role of histone deacetylase 1 (HDAC1) on HTLV-1 gene expression from an integrated template. First we show that trichostatin A, an HDAC inhibitor, enhances Tax expression in HTLV-1-transformed cells. Second, using a cell line containing a single-copy HTLV-1 long terminal repeat, we demonstrate that overexpression of HDAC1 represses Tax transactivation. Furthermore, a chromatin immunoprecipitation assay allowed us to analyze the interaction of transcription factors, coactivators, and HDACs with the basal and activated HTLV-1 promoter. We demonstrate that HDAC1 is associated with the inactive, but not the Tax-transactivated, HTLV-1 promoter. In vitro and in vivo glutathione S-transferase-Tax pull-down and coimmunoprecipitation experiments demonstrated that there is a direct physical association between Tax and HDAC1. Importantly, biotinylated chromatin pull-down assays demonstrated that Tax inhibits and/or dissociates the binding of HDAC1 to the HTLV-1 promoter. Our results provide evidence that Tax interacts directly with HDAC1 and regulates binding of the repressor to the HTLV-1 promoter.
Lu
Hanxin
H
Virus Tumor Biology Section, Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Pise-Masison
Cynthia A
CA
Linton
Rebecca
R
Park
Hyeon Ung
HU
Schiltz
R Louis
RL
Sartorelli
Vittorio
V
Brady
John N
JN
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D002843:Chromatin; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000821:virology; D020079:Terminal Repeat Sequences / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002843:Chromatin; D004791:Enzyme Inhibitors; D016356:Gene Products, tax; D006877:Hydroxamic Acids; C012589:trichostatin A; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases