PAX6, a "master gene" for eye development: Target genes and mechanism of action

A. Cvekl, F. Kashanchi, J. Epstein, M. Rauchman, R. Maas, J. Piatigorsky

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Purpose. Pax-6 is a transcription factor that is essential for eye development in vertebrates and Drosophila. Mutations of the Pax-6 gene have been shown to result in numerous eye abnormalities. The present study is designed to determine the molecular mechanisms of Pax-6 function. Methods. Mutagenesis, DNA-binding and cotransfection experiments have indicated that Pax-6 is involved in the lens-specific expression of many crystallin genes. The structure of Pax-6 binding sites was studied in detail using purified variants of Pax-6. Interactions of Pax-6 with other transcription factors (TFIID, TFIIB, pRB and p53) were studied immunologically. Results and Conclusions. We have found that two synthetic Pax-6 binding sites from the chicken αA- and δ1-crystallin genes are recognized by the canonical (128 aa) as well as an alternatively spliced 142 aa paired domain. The Pax-6 homeodomain (Prd type with Ser50) provides a surface for interaction with the general transcription factor TFIID via its component TBP (TATA-box binding protein). Ongoing experiments are designed to understand the functional significance and conservation of this property within the Pax family of factors. Results from this study provide new insights into the molecular mechanism of Pax-6 and improve prediction of its target genes.

Original languageEnglish (US)
Pages (from-to)S150
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Cvekl, A., Kashanchi, F., Epstein, J., Rauchman, M., Maas, R., & Piatigorsky, J. (1996). PAX6, a "master gene" for eye development: Target genes and mechanism of action. Investigative Ophthalmology and Visual Science, 37(3), S150.