Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development

Yusuke Kamachi*, Masanori Uchikawa, Aki Tanouchi, Ryohei Sekido, Hisato Kondoh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Pax6 is a key transcription factor in eye development, particularly in lens development, but its molecular action has not been clarified. We demonstrate that Pax6 initiates lens development by forming a molecular complex with SOX2 on the lens-specific enhancer elements, e.g., the δ-crystallin minimal enhancer DC5. DC5 shows a limited similarity to the binding consensus sequence of Pax6 and is bound poorly by Pax6 alone. However, Pax6 binds cooperatively with SOX2 to the DC5 sequence, resulting in formation of a high-mobility form of ternary complex in vitro, which correlates with the enhancer activation in vivo. We observed Pax6 and SOX2-interdependent factor occupancy of DC5 in a chromatin environment in vivo, providing the molecular basis of synergistic activation by Pax6 and SOX2. Subtle alterations of the Pax6-binding-site sequence of DC5 or of the inter-binding-sites distance diminished the cooperative binding and caused formation of a non-functional low-mobility form complex, suggesting DNA sequence-guided and protein interaction-induced conformation change of the Pax6 protein. When ectopically expressed in embryo ectoderm, Pax6 and SOX2 in combination activate δ-crystallin gene and elicit lens placode development, indicating that the complex of Pax6 and SOX2 formed on specific DNA sequences is the genetic switch for initiation of lens differentiation.

Original languageEnglish
Pages (from-to)1272-1286
Number of pages15
JournalGenes and Development
Issue number10
Publication statusPublished - 15 May 2001


  • expression cloning
  • lens induction
  • lens placode
  • Pax6
  • Sox2
  • transcriptional synergy


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