Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid

Asian Pac J Trop Med. 2013 Jun;6(6):473-80. doi: 10.1016/S1995-7645(13)60077-2.

Abstract

Objective: To identify target genes of transcription factor CCAAT enhancer-binding protein β (CEBPB) in acute promyelocytic leukemia cells induced by all-trans retinoic acid.

Methods: A new strategy for high-throughput identification of direct target genes was established by combining chromatin immunoprecipitation (ChIP) with in vitro selection. Then, 106 potential CEBPB binding fragments from the genome of the all-trans retinoic acid (ATRA)-treated NB4 cells were identified.

Results: Of them, 82 were mapped in proximity to known or previously predicted genes; 7 were randomly picked up for further confirmation by ChIP-PCR and 3 genes (GALM, ITPR2 and ORM2) were found to be specifically up-regulated in the ATRA-treated NB4 cells, indicating that they might be the down-stream target genes of ATRA.

Conclusions: Our results provided new insight into the mechanisms of ATRA-induced granulocytic differentiation.

MeSH terms

  • Binding Sites
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line
  • Chromatin Immunoprecipitation
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Tretinoin / pharmacology*

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Tretinoin