c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter

J Virol. 2007 Oct;81(20):10914-23. doi: 10.1128/JVI.01208-07. Epub 2007 Aug 1.


Histone deacetylase (HDAC) inhibitors such as valproic acid (VPA) induce the expression of quiescent proviral human immunodeficiency virus type 1 (HIV-1) and may deplete proviral infection in vivo. To uncover novel molecular mechanisms that maintain HIV latency, we sought cellular mRNAs whose expression was diminished in resting CD4(+) T cells of HIV-1-infected patients exposed to VPA. c-Myc was prominent among genes markedly downregulated upon exposure to VPA. c-Myc expression repressed HIV-1 expression in chronically infected cell lines. Chromatin immunoprecipitation (ChIP) assays revealed that c-Myc and HDAC1 are coordinately resident at the HIV-1 long terminal repeat (LTR) promoter and absent from the promoter after VPA treatment in concert with histone acetylation, RNA polymerase II recruitment, and LTR expression. Sequential ChIP assays demonstrated that c-Myc, Sp1, and HDAC1 coexist in the same DNA-protein complex at the HIV promoter. Short hairpin RNA inhibition of c-Myc reduces both c-Myc and HDAC1 occupancy, blocks c-Myc repression of Tat activation, and increases LTR expression. These results expand the understanding of mechanisms that recruit HDAC and maintain the latency of HIV-1, suggesting novel therapeutic approaches against latent proviral HIV infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • HIV Long Terminal Repeat
  • HIV-1 / genetics*
  • Histone Deacetylase 1
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / metabolism*
  • Humans
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Sp1 Transcription Factor / genetics*
  • Valproic Acid / pharmacology
  • Virus Latency* / drug effects


  • Histone Deacetylase Inhibitors
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Sp1 Transcription Factor
  • Valproic Acid
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases