Genome-wide analysis of POU3F2/BRN2 promoter occupancy in human melanoma cells reveals Kitl as a novel regulated target gene

Pigment Cell Melanoma Res. 2010 Jun;23(3):404-18. doi: 10.1111/j.1755-148X.2010.00697.x. Epub 2010 Mar 17.


POU3F2 is a POU-Homeodomain transcription factor expressed in neurons and melanoma cells. In melanoma lesions, cells expressing high levels of POU3F2 show enhanced invasive and metastatic capacity that can in part be explained by repression of Micropthalmia-associated Transcription Factor (MITF) expression via POU3F2 binding to its promoter. To identify other POU3F2 target genes that may be involved in modulating the properties of melanoma cells, we performed ChIP-chip experiments in 501Mel melanoma cells. 2108 binding loci located in the regulatory regions of 1700 potential target genes were identified. Bioinformatic and experimental assays showed the presence of known POU3F2-binding motifs, but also many AT-rich sequences with only partial similarity to the known motifs at the occupied loci. Functional analysis indicates that POU3F2 regulates the stem cell factor (Kit ligand, Kitl) promoter via a cluster of four closely spaced binding sites located in the proximal promoter. Our results suggest that POU3F2 may regulate the properties of melanoma cells via autocrine KIT ligand signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Base Sequence
  • Binding Sites
  • CD36 Antigens / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Genes, Neoplasm / genetics
  • Genetic Loci / genetics
  • Genome, Human / genetics*
  • Genome-Wide Association Study*
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics*
  • Humans
  • Melanoma / genetics*
  • Melanoma / pathology
  • Microphthalmia-Associated Transcription Factor / genetics
  • Molecular Sequence Data
  • POU Domain Factors / chemistry
  • POU Domain Factors / genetics*
  • Promoter Regions, Genetic*
  • Protein Binding
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Stem Cell Factor / genetics*
  • Transcriptional Activation / genetics
  • Wnt Proteins / genetics


  • CD36 Antigens
  • Homeodomain Proteins
  • Microphthalmia-Associated Transcription Factor
  • POU Domain Factors
  • Stem Cell Factor
  • WNT16 protein, human
  • Wnt Proteins
  • transcription factor Brn-2