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Title: Regulation of the 5'-flanking region of the human CYP27B1 gene in osteoblast cells.
Austin Authors: Turner, A G;Dwivedi, P P;Anderson, Paul H;May, B K;Morris, Howard A
Affiliation: Department of Medicine, Austin Health, University of Melbourne, Australia
Issue Date: 11-Jun-2009
Publication information: Molecular and Cellular Endocrinology 2009; 311(1-2): 55-61
Abstract: Synthesis of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is catalysed by the enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (CYP27B1). Regulation of CYP27B1 gene expression is poorly understood, particularly in non-renal tissues including bone where 1,25(OH)(2)D(3) is hypothesised to serve autocrine/paracrine roles. Transient transfection of ROS 17/2.8 osteoblast-like cells with reporter gene constructs containing deletions of the 5'-flanking region of the human CYP27B1 gene revealed a proximal promoter, enhancer region and strong upstream repressive region. Putative CCAAT and GC boxes, as well as Ets protein binding sites were shown to contribute to promoter and enhancer activities respectively in common with kidney and prostate cells. Inhibition of basal expression was largely attributed to a palindrome 5'-GTCTCAGAC-3' (-1015/-1007bp) that contains two putative canonical Smad binding elements. We conclude that repression of CYP27B1 gene expression may be a common event but the novel inhibitory elements we have identified may be unique to osteoblasts.
Gov't Doc #: 19524013
DOI: 10.1016/j.mce.2009.06.001
Type: Journal Article
Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase.genetics
5' Flanking Region.genetics
Base Sequence
Cell Line, Tumor
DNA Mutational Analysis
Enhancer Elements, Genetic.genetics
Gene Expression Regulation.drug effects
Molecular Sequence Data
Osteoblasts.drug effects.enzymology
Promoter Regions, Genetic.genetics
Sequence Deletion
Transforming Growth Factor beta.pharmacology
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