title: Prg1 is regulated by the basic helix-loop-helix transcription factor Math2.
abstract: Math2 (NEX-1/NeuroD6) is a member of the basic helix-loop-helix transcription factor family and is involved in neuronal differentiation and maturation. In this study, we identified the genes targeted by Math2 using DNA microarrays and cultured rat cortical cells transfected with Math2. Of the genes regulated by Math2, we focused on plasticity-related gene 1 (Prg1). Prg1 expression induced by Math2 was confirmed in cultured rat cortical cells and PC12 cells analyzed by real-time quantitative PCR. In the promoter region of rat Prg1, we identified four E-boxes [designated -E1 to -E4 (CANNTG)] recognized by the basic helix-loop-helix transcription factor. Using chromatin immunoprecipitation assays, we found that Math2 directly bound to at least one of these E-boxes. The Prg1 reporter assay showed that -E1 was critical for the regulation of Math2-mediated Prg1 expression. Investigation of the functional roles of Math2 and Prg1 in PC12 cells revealed that 72 h after transfection with either Math2 or Prg1, neurite length and number were significantly induced. Co-transfection with Prg1-siRNA completely inhibited Math2-mediated morphological changes. Our results suggest that Math2 directly regulates Prg1 expression and that the Math2-Prg1 cascade plays an important role in neurite outgrowth in PC12 cells.
authors.affiliation: Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Yamada
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Shida
authors.forename: Kou
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanioka
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Takashi
authors.initials: T
authors.lastname: Tobe
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D024721:E-Box Elements / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002148:Calmodulin-Binding Proteins; D010744:Phosphoric Monoester Hydrolases; D014157:Transcription Factors; C490554:Neurod6 protein, rat; C476330:Plppr4 protein, rat