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

2005 ◽  
Vol 328 (4) ◽  
pp. 831-837 ◽  
Author(s):  
T. Jääskeläinen ◽  
J. Huhtakangas ◽  
P.H. Mäenpää
Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3409-3416 ◽  
Author(s):  
Alexander P. Alimov ◽  
Ok-Kyong Park-Sarge ◽  
Kevin D. Sarge ◽  
Hartmut H. Malluche ◽  
Nicholas J. Koszewski

Abstract 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.


FEBS Letters ◽  
2000 ◽  
Vol 480 (2-3) ◽  
pp. 84-88 ◽  
Author(s):  
Eeva Martelin ◽  
Jorma J. Palvimo ◽  
Risto Lapatto ◽  
Kari O. Raivio

2003 ◽  
Vol 371 (2) ◽  
pp. 265-275 ◽  
Author(s):  
Marta NICOLÁS ◽  
Vèronique NOÉ ◽  
Carlos J. CIUDAD

We analysed in detail the minimal promoter of transcription factor Sp1, which extends 217bp from the initiation of transcription. Within this sequence we identified putative binding sites for Sp1, nuclear factor Y (NF-Y), activator protein 2 ('AP-2'), CCAAT/enhancer-binding protein ('C/EBP') and E2F transcription factors. In one case, the boxes for Sp1 and NF-Y are overlapping. Gel-shift and supershift assays demonstrated specific binding of Sp1, Sp3 and NF-Y proteins. Transient transfections and luciferase assays revealed activation of the Sp1 minimal promoter upon overexpression of Sp1 itself, NF-Y and E2F. Whereas overexpression of NF-Y or E2F had an additive effect on Sp1 overexpression, the activation of Sp1 transcription due to Sp1 was counteracted by Sp3 overexpression. Mutagenesis analysis of the NFY/Sp1-overlapping box revealed that both factors compete for this box, and that when the NF-Y site of this overlapping box is specifically mutated there is an increase in Sp1 binding, thus increasing transcriptional activity. These results help to explain the complex regulation of the Sp1 gene, which depends on the relative amounts of Sp1, Sp3, E2F and NF-Y proteins in the cell.


Endocrinology ◽  
2004 ◽  
Vol 145 (6) ◽  
pp. 2713-2720 ◽  
Author(s):  
Alexander P. Alimov ◽  
M. Chris Langub ◽  
Hartmut H. Malluche ◽  
Ok-Kyong Park-Sarge ◽  
Nicholas J. Koszewski

1973 ◽  
Vol 71 (4_Suppl) ◽  
pp. S163
Author(s):  
R. Hehrmann ◽  
E. Jentsch ◽  
H. Mayer ◽  
R. Montz

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