Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y.
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.
Jääskeläinen
T
T
Department of Biochemistry, University of Kuopio, FIN-70211 Kuopio, Finland. tiinamari.jaaskelainen@uku.fi
Huhtakangas
J
J
Mäenpää
P H
PH
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
D023081:CCAAT-Binding Factor; C470125:PTH protein, human; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D014157:Transcription Factors; C402244:nuclear factor Y; D002762:Cholecalciferol