title: Disruption of polycomb repressor complex-mediated gene silencing reactivates HIV-1 provirus in latently infected cells.
abstract: OBJECTIVE
  Persistent HIV-1 infections are characterized by a long silent infection period in resting CD4+ T cells, which allows them to escape the host immune response. Several HIV-1 latency mechanisms have been reported, but the molecular mechanism underlying polycomb repressor complex (PRC)-mediated HIV-1 latency remains poorly understood.
  
  
  METHODS
  Expression of PRC proteins in latent cells was measured by Western blot. Knockdowns of PRC genes were conducted by the specific siRNA and methylations at H3K27 on the proviral LTR were investigated by ChIP assay.
  
  
  RESULTS
  PRC proteins (EED, BMI-1, and RNF2) were dramatically downregulated in latent cells after PMA treatment. The downregulation of PRC proteins was followed by a decrease in the methylation of H3K27 and ubiquitination of H2AK119 in the PMA-treated latent cells. siRNA knockdowns of EED and BMI-1 also enhanced HIV-1 reactivation significantly in latently infected cells. By contrast, proteasomal inhibitor MG132 successfully abrogated the PMA-induced downregulation of PRCs. In particular, di-/tri-methylations of histone-3 in the proviral LTR was absent from latent cells after PMA treatment.
  
  
  CONCLUSIONS
  This study shows that PRC is strongly related to the control of HIV-1 latency and that PRC-breaking agents may be helpful for purging HIV-1 from latent reservoirs.
authors.affiliation: Division of AIDS, Korea National Institute of Health, Chungbuk, Republic of Korea.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Yoon
authors.forename: Dai-Ho
authors.initials: DH
authors.lastname: Jang
authors.forename: Kyung-Chang
authors.initials: KC
authors.lastname: Kim
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Park
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Sung Soon
authors.initials: SS
authors.lastname: Kim
authors.forename: Sung-Gil
authors.initials: SG
authors.lastname: Chi
authors.forename: Byeong-Sun
authors.initials: BS
authors.lastname: Choi
mesh_terms: D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism*; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D063146:Polycomb-Group Proteins