title: Gene silencing in HIV-1 latency by polycomb repressive group.
abstract: BACKGROUND
  The persistence of latently human immunodeficiency virus-1 (HIV-1) infected cellular reservoirs in resting CD4+ T cells is a major obstacle to HIV-1 eradication. The detailed mechanism of HIV-1 latency remains unclear. We investigated histones and their post-translational modification associated with HIV-1 latency in novel HIV-1 latently infected cell lines established previously, NCHA cells.
  
  
  METHODS
  To examine histones and their modification linked with HIV-1 latency, the expression profiles for core histone proteins and histone deacetylases (HDACs) in NCHA cells were characterized by RT-PCR, ELISA, and western blot. The levels of histone acetylation and methylation at histone H3 Lys9 (H3K9) and Lys27 (H3K27) in HIV-1 latently infected cells were analyzed by western blot and chromatin immunoprecipitation-sequencing (ChIP-seq).
  
  
  RESULTS
  The expression levels for four core histone proteins (H2A, H2B, H3 and H4) and HDACs (HDAC1-8) in NCHA cells were not significantly different from those in their parental cells. Histone H3K9 and H3K27 acetylations in NCHA cells showed no difference in parental and NCHA cells, whereas the levels of di- and tri-methylation were increased in NCHA cells. The expression of EED which is a component of polycomb repressive complex 2 (PRC2), and BMI1 and RING2 which are constituents of PRC1, were upregulated in NCHA cells. In addition, more ubiquitylation at histone H2A was detected in NCHA cells.
  
  
  CONCLUSIONS
  Our results suggest that tri-methylation of histone H3K27 and H2A ubiquitylation via polycomb group protein may play a crucial role in epigenetic silencing accounting for HIV-1 latency in NCHA cells.
authors.affiliation: Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health, Chung-buk, Republic of Korea.
authors.forename: Hyeon Guk
authors.initials: HG
authors.lastname: Kim
authors.forename: Kyung-Chang
authors.initials: KC
authors.lastname: Kim
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Roh
authors.forename: Jihwan
authors.initials: J
authors.lastname: Park
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Jung
authors.forename: Joo-Shil
authors.initials: JS
authors.lastname: Lee
authors.forename: Sang-Yun
authors.initials: SY
authors.lastname: Choi
authors.forename: Sung Soon
authors.initials: SS
authors.lastname: Kim
authors.forename: Byeong-Sun
authors.initials: BS
authors.lastname: Choi
mesh_terms: D000107:Acetylation; D002460:Cell Line; D005786:Gene Expression Regulation; D020868:Gene Silencing; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency
chemical_list: C491488:EED protein, human; D006657:Histones; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D063151:Polycomb Repressive Complex 2; D006655:Histone Deacetylases