title: Histone deacetylase inhibitors suppress ABO transcription in vitro, leading to reduced expression of the antigens.
abstract: The ABO system is of fundamental importance in the fields of transfusion and transplantation and has apparent associations with certain diseases, including cardiovascular disorders. ABO expression is reduced in the late phase of erythroid differentiation in vitro, whereas histone deacetylase inhibitors (HDACIs) are known to promote cell differentiation. Therefore, whether or not HDACIs could reduce the amount of ABO transcripts and A or B antigens is an intriguing issue.
  
  
  
  Quantitative polymerase chain reactions were carried out for the ABO transcripts in erythroid-lineage K562 and epithelial-lineage KATOIII cells after incubation with HDACIs, such as sodium butyrate, panobinostat, vorinostat, and sodium valproate. Flow cytometric analysis was conducted to evaluate the amounts of antigen in KATOIII cells treated with panobinostat. Quantitative chromatin immunoprecipitation (ChIP) assays and luciferase assays were performed on both cell types to examine the mechanisms of ABO suppression.
  
  
  
  HDACIs reduced the ABO transcripts in both K562 and KATOIII cells, with panobinostat exerting the most significant effect. Flow cytometric analysis demonstrated a decrease in B-antigen expression on panobinostat-treated KATOIII cells. ChIP assays indicated that panobinostat altered the modification of histones in the transcriptional regulatory regions of ABO, and luciferase assays demonstrated reduced activity of these elements.
  
  
  
  ABO transcription seems to be regulated by an epigenetic mechanism. Panobinostat appears to suppress ABO transcription, reducing the amount of antigens on the surface of cultured cells.
authors.affiliation: Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Kubo
authors.affiliation: Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Sano
authors.affiliation: Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.affiliation: Department of Hematology, University of Occupational and Environmental Health, Kitakyushu City, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Tsukada
authors.affiliation: Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kominato
mesh_terms: D000017:ABO Blood-Group System / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000017:ABO Blood-Group System; D056572:Histone Deacetylase Inhibitors