PML/RARalpha targets promoter regions containing PU.1 consensus and RARE half sites in acute promyelocytic leukemia

Cancer Cell. 2010 Feb 17;17(2):186-97. doi: 10.1016/j.ccr.2009.12.045.


PML/RARalpha is of crucial importance in acute promyelocytic leukemia (APL) both pathologically and therapeutically. Using a genome-wide approach, we identified in vivo PML/RARalpha binding sites in a PML/RARalpha-inducible cell model. Of the 2979 targeted regions, >62% contained canonical PU.1 motifs and >84% of these PU.1 motifs coexisted with one or more RARE half (RAREh) sites in nearby regions. Promoters with such PU.1-RAREh binding sites were transactivated by PU.1. PU.1-mediated transactivation was repressed by PML/RARalpha and restored by the addition of all-trans retinoic acid (ATRA). Genes containing such promoters were significantly represented by genes transcriptionally suppressed in APL and/or reactivated upon treatment with ATRA. Thus, selective targeting of PU.1-regulated genes by PML/RARalpha is a critical mechanism for the pathogenesis of APL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • Chromatin Immunoprecipitation
  • Consensus Sequence
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Molecular Sequence Data
  • Myeloid Cells / metabolism
  • Oncogene Proteins, Fusion / metabolism
  • Oncogene Proteins, Fusion / physiology*
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins / metabolism*
  • Trans-Activators / metabolism*


  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Trans-Activators
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • proto-oncogene protein Spi-1

Associated data

  • GEO/GSE19201
  • GEO/GSE19202