Transactivation of the parathyroid hormone promoter by specificity proteins and the nuclear factor Y complex.
We previously identified a highly conserved specificity protein 1 (Sp1) DNA element in mammalian PTH promoters that acted as an enhancer of gene transcription and bound Sp1 and Sp3 proteins present in parathyroid gland nuclear extracts. More recently, a nuclear factor (NF)-Y element (NF-Y(prox)) was also described by our group, which was located approximately 30 bp downstream from the Sp1 site in the human PTH (hPTH) promoter and by itself acted as a weak enhancer of gene transcription. We now report that Sp proteins and NF-Y can synergistically enhance transcription of a minimal hPTH promoter construct. Positioning of the Sp1 DNA element appears to be critical for this synergism because deviations of one half of a helical turn caused an approximate 60% decrease in transactivation. Finally, examination of the bovine PTH (bPTH) promoter also revealed Sp1/NF-Y synergism, in conjunction with the identification of an analogous NF-Y binding site similarly positioned downstream from the bPTH Sp1 element. In summary, synergistic transactivation of the hPTH and bPTH promoters is observed by Sp proteins and the NF-Y complex. The conservation of this transactivation in the human and bovine promoters suggests that this may be a principle means of enhancing PTH gene transcription.
Alimov
Alexander P
AP
University of Kentucky Medical Center, Division of Nephrology, Bone and Mineral Metabolism, Lexington, Kentucky 40536-0298, USA.
Park-Sarge
Ok-Kyong
OK
Sarge
Kevin D
KD
Malluche
Hartmut H
HH
Koszewski
Nicholas J
NJ
D000818:Animals; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D017124:Conserved Sequence; D017931:DNA Primers; D004330:Drosophila; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D016296:Mutagenesis; D010281:Parathyroid Hormone / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D023081:CCAAT-Binding Factor; D017931:DNA Primers; D010281:Parathyroid Hormone; D014157:Transcription Factors; C402244:nuclear factor Y; D008156:Luciferases