Contributions of distal and proximal promoter elements to glucocorticoid regulation of osteocalcin gene transcription

Molecular Endocrinology
F AslamJ B Lian

Abstract

Previous studies identified several glucocorticoid response elements (GREs) in the 5'-promoter region of the rat osteocalcin (OC) gene by purified receptor binding. The present study addresses functionality of the GRE sequences in the proximal promoter at nucleotide (nt) -16 to -1 downstream of the TATA element together with the GRE half-element in the OC box at nt -86 to -81. This was done by assaying glucocorticoid responsiveness [at 10(-6) M dexamethasone (DEX)], and in combination with 10(-8) M 1,25-dihydroxyvitamin D3, of a series of deleted and mutated OC promoter reporter constructs (OCCAT) in osteoblast-like cells, the ROS 17/2.8 rat osteosarcoma line. Promoter deletion analysis revealed an additional GRE in the distal promoter at nt -697 to -683 that functions to suppress OC transcription. In the absence of this upstream negative GRE (nGRE), the -531 OCCAT construct exhibited enhanced promoter activity in response to DEX (1.8-fold DEX/Control), but further deletion (-348 and -108 OCCAT constructs) restored DEX suppression to OC promoter activity (0.6- and 0.8-fold DEX/Control, respectively). Mutations introduced in both the proximal GRE (nt -16 to -1) and the half-GRE in the OC box, or in the proximal GRE alone, nearly...Continue Reading

Citations

Jan 7, 1997·Proceedings of the National Academy of Sciences of the United States of America·B GuoJ L Stein
Feb 20, 2007·Calcified Tissue International·O Akhouayri, R St-Arnaud
Mar 28, 2013·International Journal of Endocrinology·Monika Puzianowska-KuznickaJacek Polosak
Aug 24, 2019·Frontiers in Immunology·Laura Escoter-TorresSabine Vettorazzi

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