title: PAX6 Isoforms, along with Reprogramming Factors, Differentially Regulate the Induction of Cornea-specific Genes.
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.
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Sasamoto
authors.affiliation: Department of Stem Cell and Applied Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Laboratory of Functional Analysis in silico, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Laboratory of Functional Analysis in silico, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.|Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Saito-Adachi
authors.affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8568, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawasaki
authors.affiliation: Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4HQ, Wales, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Quantock
authors.affiliation: Laboratory of Functional Analysis in silico, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakai
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Tsujikawa
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishida
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D019573:Epithelium, Corneal / Q000254:growth & development / Q000378:metabolism; D005123:Eye / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053551:Keratin-12 / Q000096:biosynthesis* / Q000235:genetics; D053558:Keratin-3 / Q000096:biosynthesis* / Q000235:genetics; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis* / Q000235:genetics; D000071841:PAX6 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: C000715467:KLF4 protein, human; C507494:KRT12 protein, human; C479360:KRT3 protein, human; D053551:Keratin-12; D053558:Keratin-3; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; C494173:POU5F1 protein, human; D020033:Protein Isoforms