Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y

• Published in: Biochemical and biophysical research communications Vol. 328; no. 4; pp. 831 - 837
• Main Authors: Jääskeläinen, T, Huhtakangas, J, Mäenpää, P H
• Format: Journal Article
• Language: English
• Published: United States 25.03.2005
• Subjects: Animals; Binding Sites; CCAAT-Binding Factor - metabolism; Cell Line; Cholecalciferol - genetics; Cholecalciferol - metabolism; Down-Regulation - drug effects; Down-Regulation - physiology; Humans; Parathyroid Hormone - analogs & derivatives; Parathyroid Hormone - genetics; Parathyroid Hormone - metabolism; Pituitary Gland - metabolism; Promoter Regions, Genetic; Protein Binding; Rats; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; Transcription Factors - metabolism; Transcriptional Activation - physiology; Vitamin D Response Element - genetics
• ISSN: 0006-291X
• DOI: 10.1016/j.bbrc.2005.01.033

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.