title: Induction of human fetal hemoglobin expression by adenosine-2',3'-dialdehyde.
abstract: BACKGROUND
  Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2',3'-dialdehyde (Adox) on induction of human fetal hemoglobin (HbF) in K562 cells and human hematopoietic progenitor cells.
  
  
  METHODS
  Expression levels of human fetal hemoglobin were assessed by northern blot analysis and Real-time PCR. HbF and adult hemoglobin (HbA) content were analyzed using high-performance liquid chromatography (HPLC). DNA methylation levels on human gamma-globin gene promoters were determined using Bisulfite sequence analysis. Enrichment of histone marks on genes was assessed by chromosome immunoprecipitation (ChIP).
  
  
  RESULTS
  Adox induced γ-globin gene expression in both K562 cells and in human bone marrow erythroid progenitor cells through a mechanism potentially involving inhibition of protein arginine methyltransferase 5 (PRMT5).
  
  
  CONCLUSIONS
  The ability of methyl transferase inhibitors such as Adox to efficiently reactivate fetal hemoglobin expression suggests that these agents may provide a means of reactivating fetal globin expression as a therapeutic option for treating sickle cell disease and β-thalassemia.
authors: Molecular Immunology and Cancer Research Center, The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China. stephen.jane@monash.edu
authors: Yinghong
authors: Y
authors: He
authors: Gerhard
authors: G
authors: Rank
authors: Miaomiao
authors: M
authors: Zhang
authors: Junyi
authors: J
authors: Ju
authors: Ronghua
authors: R
authors: Liu
authors: Zhen
authors: Z
authors: Xu
authors: Fiona
authors: F
authors: Brown
authors: Loretta
authors: L
authors: Cerruti
authors: Chi
authors: C
authors: Ma
authors: Renxiang
authors: R
authors: Tan
authors: Stephen M
authors: SM
authors: Jane
authors: Quan
authors: Q
authors: Zhao
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015152:Blotting, Northern; D047369:Chromatin Immunoprecipitation; D002851:Chromatography, High Pressure Liquid; D005319:Fetal Hemoglobin / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C027579:periodate-oxidized adenosine; D005319:Fetal Hemoglobin; D000241:Adenosine