Transactivation of the parathyroid hormone promoter by specificity proteins and the nuclear factor Y complex.

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-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.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Alimov AP,Park-Sarge OK,Sarge KD,Malluche HH,Koszewski NJ

doi

10.1210/en.2005-0272

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

3409-16

issue

8

eissn

0013-7227

issn

1945-7170

pii

en.2005-0272

journal_volume

146

pub_type

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