title: Search for regulatory factors of the pituitary-specific transcription factor PROP1 gene.
abstract: 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.
authors.affiliation: Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa 214-8571, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nishimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueharu
authors.forename: Hiroto
authors.initials: H
authors.lastname: Nishihara
authors.forename: Shiori
authors.initials: S
authors.lastname: Shibuya
authors.forename: Saishu
authors.initials: S
authors.lastname: Yoshida
authors.forename: Masashi
authors.initials: M
authors.lastname: Higuchi
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanno
authors.forename: Kotaro
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Takako
authors.initials: T
authors.lastname: Kato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007438:Introns; D051379:Mice; D038081:Organogenesis; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
chemical_list: D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D055748:SOXB1 Transcription Factors