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

抄録

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.

収録刊行物

• Genes & Development

  Genes & Development 15 (10), 1272-1286, 2001-05-15

  Cold Spring Harbor Laboratory

キーワード

• Developmental Biology
• Genetics

詳細情報

• CRID: 1363388844904725760
• NII論文ID: 80012541760
• DOI: 10.1101/gad.887101
• ISSN: 15495477
• ISSN: 08909369
• Web Site: https://syndication.highwire.org/content/doi/10.1101/gad.887101
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