title: Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y.
abstract: The negative regulation of the human parathyroid hormone (PTH) gene by biologically active vitamin D3 (1,25-dihydroxyvitamin D3; 1,25(OH)2D3) was studied in rat pituitary GH4C1 cells, which express factors needed for the negative regulation. We report here that NF-Y binds to sequences downstream of the site previously reported to bind the vitamin D receptor (VDR). Additional binding sites for NF-Y reside in the near vicinity and were shown to be important for full activity of the PTH gene promoter. VDR and NF-Y were shown to exhibit mutually exclusive binding to the VDRE region. According to our results, sequestration of binding partners for NF-Y by VDR also affects transcription through a NF-Y consensus binding element in GH4C1 but not in ROS17/2.8 cells. These results indicate that 1,25(OH)2D3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y.
authors.affiliation: Department of Biochemistry, University of Kuopio, FIN-70211 Kuopio, Finland. tiinamari.jaaskelainen@uku.fi
authors.forename: T
authors.initials: T
authors.lastname: Jääskeläinen
authors.forename: J
authors.initials: J
authors.lastname: Huhtakangas
authors.forename: P H
authors.initials: PH
authors.lastname: Mäenpää
mesh_terms: D000818:Animals; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D002460:Cell Line; D002762:Cholecalciferol / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D010281:Parathyroid Hormone / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D030181:Vitamin D Response Element / Q000235:genetics
chemical_list: D023081:CCAAT-Binding Factor; C470125:PTH protein, human; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D014157:Transcription Factors; C402244:nuclear factor Y; D002762:Cholecalciferol