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Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors.

The class III POU gene brn-2, encoding the Brn-2/N-Oct-3 transcription factor, is widely expressed in the developing mammalian central nervous system. Brn-2 has also been found to regulate the melanocytic phenotype with N-Oct-3 DNA binding activity elevated in malignant melanoma, however, its mode of action is yet to be defined. The functional role of the Brn-2 transcription factor has been investigated through the analysis of protein-protein interactions it forms with a number of basal and melanocytic transcriptional regulatory proteins. In vivo interactions were tested by gene-cotransfection using the mammalian GAL4-Herpes Simplex viral protein 16 (VP16) two hybrid formation and direct protein binding by in vitro glutathione S-transferase (GST)-pull down assay. The Brn-2 protein was found to homodimerize in vivo with high affinity, using Brn-2 deletion constructs dimer complex formation was found to be dependent on the presence of both the homeodomain and linker regions of the POU-domain. However, the POU-homoedomain was dispensable for the formation of the dimerization interface in one of the partner molecules but not both, when the POU-linker region was removed the ability to interact was lost irrespective of the presence of the homeodomain. Dimerization of Brn-2/N-Oct-3 was also found to occur in DNA binding assays using melanoma cell line nuclear extracts and a recently reported dimer target sequence probe, which may have significant consequences for gene regulation in melanocytic tumours. Low affinity Brn-2 protein contacts have also been found with the basal transcription complex, including TATA binding protein (TBP) and the transcriptional coactivator p300, and with the Sox-10 and Pax-3 transcription factors that are known to play an important role in melanocyte cell formation.

Pubmed ID: 11029584


  • Smit DJ
  • Smith AG
  • Parsons PG
  • Muscat GE
  • Sturm RA


European journal of biochemistry / FEBS

Publication Data

November 22, 2000

Associated Grants


Mesh Terms

  • Binding Sites
  • Cell Extracts
  • DNA
  • DNA-Binding Proteins
  • Dimerization
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Humans
  • Melanoma
  • Nuclear Proteins
  • Octamer Transcription Factor-3
  • POU Domain Factors
  • Paired Box Transcription Factors
  • Protein Binding
  • Protein Structure, Tertiary
  • SOXE Transcription Factors
  • Sequence Deletion
  • TATA-Box Binding Protein
  • Templates, Genetic
  • Trans-Activators
  • Transcription Factor TFIIB
  • Transcription Factors
  • Tumor Cells, Cultured