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

Citation
Y. Kamachi et al., Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development, GENE DEV, 15(10), 2001, pp. 1272-1286
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
GENES & DEVELOPMENT
ISSN journal
0890-9369 → ACNP
Volume
15
Issue
10
Year of publication
2001
Pages
1272 - 1286
Database
ISI
SICI code
0890-9369(20010515)15:10<1272:PASFAC>2.0.ZU;2-M
Abstract
Pax6 is a key transcription factor in eye development, particularly in lens development, but its molecular action has not been clarified. We demonstra te that Pax6 initiates lens development by forming a molecular complex with SOX2 on the lens-specific enhancer elements, e.g., the delta -crystallin m inimal enhancer DC5. DC5 shows a limited similarity to the binding consensu s sequence of Pax6 and is bound poorly by Pax6 alone. However, Pax6 binds c ooperatively with SOX2 to the DC5 sequence, resulting in formation of a hig h-mobility form of ternary complex in vitro, which correlates with the enha ncer activation in vivo. We observed Pax6 and SOX2-interdependent factor oc cupancy 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 d iminished the cooperative binding and caused formation of a non-functional low-mobility form complex, suggesting DNA sequence-guided and protein inter action-induced conformation change of the Pax6 protein. When ectopically ex pressed in embryo ectoderm, Pax6 and SOX2 in combination activate delta -cr ystallin gene and elicit lens placode development, indicating that the comp lex of Pax6 and SOX2 formed on specific DNA sequences is the genetic switch for initiation of lens differentiation.