Search for regulatory factors of the pituitary-specific transcription factor PROP1 gene

  • NISHIMURA Naoto
    Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • UEHARU Hiroki
    Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa 214-8571, Japan Research Fellow of the Japan Society for the Promotion of Science
  • NISHIHARA Hiroto
    Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • SHIBUYA Shiori
    Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • YOSHIDA Saishu
    Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa 214-8571, Japan Research Fellow of the Japan Society for the Promotion of Science
  • HIGUCHI Masashi
    Institute of Reproduction and Endocrinology, Meiji University, Kanagawa 214-8571, Japan
  • KANNO Naoko
    Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • HORIGUCHI Kotaro
    Laboratory of Anatomy and Cell Biology, Department of Health Sciences, Kyorin University, Tokyo 192-8508, Japan
  • KATO Takako
    Institute of Reproduction and Endocrinology, Meiji University, Kanagawa 214-8571, Japan
  • KATO Yukio
    Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa 214-8571, Japan Department of Life Science, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan Institute of Reproduction and Endocrinology, Meiji University, Kanagawa 214-8571, Japan

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Pituitary-specific transcription factor PROP1, a factor important for pituitary organogenesis, appears on rat embryonic day 11.5 (E11.5) in SOX2-expressing stem/progenitor cells and always coexists with SOX2 throughout life. PROP1-positive cells at one point occupy all cells in Rathke’s pouch, followed by a rapid decrease in their number. Their regulatory factors, except for RBP-J, have not yet been clarified. This study aimed to use the 3 kb upstream region and 1st intron of mouse prop1 to pinpoint a group of factors selected on the basis of expression in the early pituitary gland for expression of Prop1. Reporter assays for SOX2 and RBP-J showed that the stem/progenitor marker SOX2 has cell type-dependent inhibitory and activating functions through the proximal and distal upstream regions of Prop1, respectively, while RBP-J had small regulatory activity in some cell lines. Reporter assays for another 39 factors using the 3 kb upstream regions in CHO cells ultimately revealed that 8 factors, MSX2, PAX6, PIT1, PITX1, PITX2, RPF1, SOX8 and SOX11, but not RBP-J, regulate Prop1 expression. Furthermore, a synergy effect with SOX2 was observed for an additional 10 factors, FOXJ1, HES1, HEY1, HEY2, KLF6, MSX1, RUNX1, TEAD2, YBX2 and ZFP36Ll, which did not show substantial independent action. Thus, we demonstrated 19 candidates, including SOX2, to be regulatory factors of Prop1 expression.

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