PAX6 and SOX2-dependent regulation of the Sox2 enhancer N-3 involved in embryonic visual system development

Genes Cells. 2007 Sep;12(9):1049-61. doi: 10.1111/j.1365-2443.2007.01114.x.


Sox2 is universally expressed in the neural and placodal primordia in early stage embryos, and this expression depends on various phylogenetically conserved enhancers having different regional and temporal specificities. The enhancer N-3 was identified as a regulator of the Sox2 gene active in the diencephalon, optic vesicle, and after the contact of the vesicle with the ectoderm, in the lens placodal surface area, suggesting its involvement in embryonic visual system development. A 36-bp minimal essential core sequence was defined in the 568-bp-long enhancer N-3, which in a tetrameric form emulates the original enhancer activity. The core sequence comprises a SOX-binding sequence and a non-canonical PAX6 (Paired domain) binding sequence, and is activated by the synergistic action of SOX2 and PAX6 in transfected cells. The SOX and PAX6 binding sequences of the N-3 core are arranged with the same orientation and spacing as the DC5 sequence of the delta-crystallin enhancer previously demonstrated to be cooperatively bound by SOX2 and PAX6. The N-3 core sequence was also bound by these factors in a cooperative fashion, but with a higher threshold of these factors' levels than DC5, and the enhancer effect of the tetrameric sequence activated by exogenous SOX2 and PAX6 was less pronounced than that of DC5. The observations suggest that gene activation mechanisms that depend on the cooperative interaction of SOX2 and PAX6 but with different thresholds of the factor levels are crucial for the regulation of visual system development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chick Embryo
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Embryonic Induction / genetics
  • Enhancer Elements, Genetic*
  • Epithelial Cells / metabolism
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Gene Expression Regulation, Developmental*
  • HMGB Proteins / genetics*
  • HMGB Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Lens, Crystalline / embryology*
  • Mice
  • Models, Biological
  • Models, Genetic
  • Molecular Sequence Data
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • SOXB1 Transcription Factors
  • Sequence Alignment
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection
  • delta-Crystallins / genetics
  • delta-Crystallins / metabolism


  • DNA-Binding Proteins
  • Eye Proteins
  • HMGB Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Recombinant Proteins
  • Repressor Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Transcription Factors
  • delta-Crystallins