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-Yprox) was a...

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Published in:Endocrinology (Philadelphia) 2005-08, Vol.146 (8), p.3409-3416
Main Authors: Alimov, Alexander P, Park-Sarge, Ok-Kyong, Sarge, Kevin D, Malluche, Hartmut H, Koszewski, Nicholas J
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological and medical sciences
Cattle
CCAAT-Binding Factor - genetics
CCAAT-Binding Factor - metabolism
CCAAT-Binding Factor - physiology
Cell Line
Conserved Sequence
DNA Primers
Drosophila
Fundamental and applied biological sciences. Psychology
Genes, Reporter
Humans
Luciferases - genetics
Mutagenesis
Parathyroid Hormone - genetics
Polymerase Chain Reaction
Promoter Regions, Genetic
Transcription Factors - physiology
Transcriptional Activation
Vertebrates: endocrinology
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Summary: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-Yprox) 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.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2005-0272