Analysis of Basal Regulatory Elements in the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene Promoter

“…All reporter constructs utilized in this study were described previously [15] and were kindly provided by Dr. Hector DeLuca (University of Wisconsin, Madison). The ␤-galactosidase expression plasmid was obtained from Michael Rauchman (Washington University).…”

Section: Plasmids Antibodiesmentioning

confidence: 99%

1α-Hydroxylase transactivation by γ-interferon in murine macrophages requires enhanced C/EBPβ expression and activation

Esteban

Vidal

Dusso

2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…In the human 1␣(OH)ase promoter, an SP1 site involved in basal expression and a negative vitamin D response element, which associates with VDR/retinoid X receptor as well as histone deacetylase complex in the presence of 1,25(OH) 2 D 3 , have been reported (27,28). Regions of the mouse 1␣(OH)ase promoter that contribute to its basal activity have also been characterized (29). Differences between the mouse and human promoter have been noted, suggesting different regulation of the two genes (27,29,30).…”

mentioning

confidence: 99%

“…Regions of the mouse 1␣(OH)ase promoter that contribute to its basal activity have also been characterized (29). Differences between the mouse and human promoter have been noted, suggesting different regulation of the two genes (27,29,30). Although responsiveness to PTH has been noted for both the mouse and human promoter (7-9, 30), a direct inhibition of the activity of the mouse 1␣(OH)ase promoter by 1,25(OH) 2 D 3 has not been observed (7).…”

mentioning

confidence: 99%

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Zhong

Armbrecht

Christakos

2009

Journal of Biological Chemistry

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Although parathyroid hormone (PTH) induces 25-hydroxyvitamin D 3 (25(OH)D 3 ) 1␣-hydroxylase (1␣(OH)ase) underhypocalcemic conditions, previous studies showed that calcitonin, not PTH, has an important role in the maintenance of serum 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) under normocalcemic conditions. In this study we report that 1␣(OH)ase transcription is strongly induced by calcitonin in kidney cells and indicate mechanisms that underlie this regulation. The transcription factor C/EBP␤ is up-regulated by calcitonin in kidney cells and results in a significant enhancement of calcitonin induction of 1␣(OH)ase transcription and protein expression. Mutation constructs of the 1␣(OH)ase promoter demonstrate the importance of the C/EBP␤ binding site at ؊79/؊73 for activation of the 1␣(OH)ase promoter by calcitonin. The SWI/SNF chromatin remodeling complex was found to cooperate with calcitonin in the regulation of 1␣(OH)ase. Chromatin immunoprecipitation analysis showed that calcitonin recruits C/EBP␤ to the 1␣(OH)ase promoter, and Re-chromatin immunoprecipitation analysis (sequential chromatin immunoprecipitations using different antibodies) showed that C/EBP␤ and BRG1, an ATPase that is a component of the SWI/SNF complex, bind simultaneously to the 1␣(OH)ase promoter. These findings are the first to address the dynamics between calcitonin, C/EBP␤, and SWI/SNF in the regulation of 1␣(OH)ase and provide a mechanism, for the first time, for calcitonin induction of 1␣(OH)ase. Because plasma calcitonin as well as 1,25(OH) 2 D 3 have been reported to be increased during pregnancy and lactation and in early development, these findings suggest a mechanism that may account, at least in part, for the increase in plasma 1,25(OH) 2 D 3 during these times of increased calcium requirement.Vitamin D is a principal factor required for maintaining normal calcium homeostasis (1). The active form of vitamin D,3 is generated by two successive hydroxylations; 25-hydroxylation in the liver and 1␣-hydroxylation in the kidney (1-3). Inactivating mutations in the 25-hydroxvitamin D 3 1␣-hydroxylase (1␣(OH)ase) gene result in vitamin D dependent rickets type I despite normal intake of vitamin D, indicating the importance of the 1␣(OH)ase enzyme (4, 5). Elevated parathyroid hormone (PTH) resulting from hypocalcemia is a primary signal mediating the renal synthesis of 1,25(OH) 2 D 3 (6). PTH stimulates 1␣(OH)ase transcription, resulting in increased 1,25(OH) 2 D 3 synthesis (7-9). However, under normocalcemic conditions, PTH fails to stimulate 1␣(OH)ase expression (10). Previous studies showed that calcitonin can enhance renal conversion of 25(OH)D 3 to 1,25(OH) 2 D 3 and that calcitonin, not PTH, is the major regulator of 1␣(OH)ase in the normocalcemic state (10 -13). In early development and during pregnancy and lactation calcitonin levels are increased under normocalcemic conditions and correlated to an increase in serum 1,25(OH) 2 D 3 levels (14 -17). The stimulation of 1,25(OH) 2 D 3 under normocalcemic conditions by calcitonin m...

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“…Recently, two consensus VDRE‐responsive sites have been identified in the human CYP27B1 promoter 58 . Still, an indirect mechanism interfering with the PTH‐induced signaling cascade might play a role 59 . Furthermore, low calcium concentrations directly stimulate CYP27B1 synthesis via activation of protein kinase C and MAPK pathways by a calcium‐sensing receptor protein 7 .…”

Section: Regulation Of Vitamin D Metabolismmentioning

confidence: 99%

Regulation of vitamin D homeostasis: implications for the immune system

et al. 2008

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Vitamin D homeostasis in the immune system is the focus of this review. The production of both the activating (25- and 1alpha-hydroxylase) and the metabolizing (24-hydroxylase) enzymes by cells of the immune system itself, indicates that 1,25(OH)(2)D(3) can be produced locally in immune reaction sites. Moreover, the strict regulation of these enzymes by immune signals is highly suggestive for an autocrine/paracrine role in the immune system, and opens new treatment possibilities.

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Analysis of Basal Regulatory Elements in the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene Promoter

Cited by 7 publications

References 11 publications

1α-Hydroxylase transactivation by γ-interferon in murine macrophages requires enhanced C/EBPβ expression and activation

1α-Hydroxylase transactivation by γ-interferon in murine macrophages requires enhanced C/EBPβ expression and activation

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Regulation of vitamin D homeostasis: implications for the immune system

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