title: Decitabine increases fetal hemoglobin in Papio anubis by increasing γ-globin gene transcription.
abstract: OBJECTIVE
  The mechanism responsible for increased fetal hemoglobin levels following decitabine treatment remains controversial. These experiments were performed to evaluate the role of transcriptional vs. translational mechanisms in the ability of decitabine to increase fetal hemoglobin levels in vivo.
  
  
  METHODS
  Three normal, nonanemic baboons were treated with decitabine subcutaneously (0.5 mg/kg/d) for 10 days. The effect of decitabine on globin chain synthesis and globin messenger RNA levels was measured in pre- and posttreatment bone marrow aspirates by biosynthetic radiolabeling with [(3)H] leucine followed by separation of globin chains by high-performance liquid chromatography, and real-time polymerase chain reaction, respectively. The effect on DNA methylation of the ɛ- and γ-globin gene promoters was determined by bisulfite sequence analysis.
  
  
  RESULTS
  Decitabine treatment of normal, nonanemic baboons induced similar increases in the γ/γ+β chain synthetic ratio and the γ/total β-like globin RNA ratio and also increased expression of ɛ-globin transcripts. Increased expression of ɛ- and γ-globin was associated with decreased DNA methylation of the ɛ- and γ-globin gene promoters.
  
  
  CONCLUSIONS
  Decitabine increases fetal hemoglobin in vivo by transcriptional activation of the γ-globin gene.
authors: Department of Medicine, University of Illinois at Chicago, and Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
authors: Imo
authors: I
authors: Akpan
authors: Virryan
authors: V
authors: Banzon
authors: Vinzon
authors: V
authors: Ibanez
authors: Kestis
authors: K
authors: Vaitkus
authors: Joseph
authors: J
authors: DeSimone
authors: Donald
authors: D
authors: Lavelle
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism; D010215:Papio; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism; D055547:epsilon-Globins / Q000235:genetics / Q000378:metabolism; D055545:gamma-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D055544:beta-Globins; D055547:epsilon-Globins; D055545:gamma-Globins; D000077209:Decitabine; D005319:Fetal Hemoglobin; D001374:Azacitidine