Role of RUNX family members in transcriptional repression and gene silencing

Oncogene. 2004 May 24;23(24):4220-4. doi: 10.1038/sj.onc.1207122.

Abstract

RUNX family members are DNA-binding transcription factors that regulate the expression of genes involved in cellular differentiation and cell cycle progression. The RUNX family includes three mammalian RUNX proteins (RUNX1, -2, -3) and two homologues in Drosophila. Experiments in Drosophila and mouse indicate that the RUNX proteins are required for gene silencing of engrailed and CD4, respectively. RUNX-mediated repression involves recruitment of corepressors such as mSin3A and Groucho as well as histone deacetylases. Furthermore, RUNX1 and RUNX3 associate with SUV39H1, a histone methyltransferase involved in gene silencing. RUNX1 is frequently targeted in human leukemia by chromosomal translocations that fuse the DNA-binding domain of RUNX1 to other transcription factors and corepressor molecules. The resulting leukemogenic fusion proteins are transcriptional repressors that form stable complexes with corepressors, histone deacetylases and histone methyltransferases. Thus, transcriptional repression and gene silencing through RUNX1 contribute to the mechanisms of leukemogenesis of the fusion proteins. Therapies directed at the associated cofactors may be beneficial for treatment of these leukemias.

Publication types

  • Review

MeSH terms

  • Animals
  • Core Binding Factor Alpha 2 Subunit
  • Core Binding Factor Alpha 3 Subunit
  • Core Binding Factor alpha Subunits
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / physiology*
  • Gene Silencing / physiology*
  • Humans
  • Mice
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic / physiology

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Core Binding Factor Alpha 3 Subunit
  • Core Binding Factor alpha Subunits
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RUNX1 protein, human
  • Runx1 protein, mouse
  • Runx3 protein, human
  • Runx3 protein, mouse
  • Transcription Factors