PAX6 Isoforms, along with Reprogramming Factors, Differentially Regulate the Induction of Cornea-specific Genes

Sci Rep. 2016 Feb 22:6:20807. doi: 10.1038/srep20807.

Abstract

PAX6 is the key transcription factor involved in eye development in humans, but the differential functions of the two PAX6 isoforms, isoform-a and isoform-b, are largely unknown. To reveal their function in the corneal epithelium, PAX6 isoforms, along with reprogramming factors, were transduced into human non-ocular epithelial cells. Herein, we show that the two PAX6 isoforms differentially and cooperatively regulate the expression of genes specific to the structure and functions of the corneal epithelium, particularly keratin 3 (KRT3) and keratin 12 (KRT12). PAX6 isoform-a induced KRT3 expression by targeting its upstream region. KLF4 enhanced this induction. A combination of PAX6 isoform-b, KLF4, and OCT4 induced KRT12 expression. These new findings will contribute to furthering the understanding of the molecular basis of the corneal epithelium specific phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Epithelial Cells / metabolism
  • Epithelium, Corneal / growth & development
  • Epithelium, Corneal / metabolism
  • Eye / growth & development*
  • Eye / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Keratin-12 / biosynthesis*
  • Keratin-12 / genetics
  • Keratin-3 / biosynthesis*
  • Keratin-3 / genetics
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / genetics
  • Octamer Transcription Factor-3 / biosynthesis*
  • Octamer Transcription Factor-3 / genetics
  • PAX6 Transcription Factor / biosynthesis
  • PAX6 Transcription Factor / genetics*
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Transduction, Genetic

Substances

  • KLF4 protein, human
  • KRT12 protein, human
  • KRT3 protein, human
  • Keratin-12
  • Keratin-3
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Octamer Transcription Factor-3
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • POU5F1 protein, human
  • Protein Isoforms