scholarly journals Large-Scale in Silico and Microarray-Based Identification of Direct 1,25-Dihydroxyvitamin D3 Target Genes

2005 ◽  
Vol 19 (11) ◽  
pp. 2685-2695 ◽  
Author(s):  
Tian-Tian Wang ◽  
Luz Elisa Tavera-Mendoza ◽  
David Laperriere ◽  
Eric Libby ◽  
Naomi Burton MacLeod ◽  
...  
Keyword(s):  
In Silico ◽  
Large Scale ◽  
Target Genes ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3

scholarly journals Retinoid X receptor:vitamin D3 receptor heterodimers promote stable preinitiation complex formation and direct 1,25-dihydroxyvitamin D3-dependent cell-free transcription.

1997 ◽  
Vol 17 (4) ◽  
pp. 1923-1937 ◽  
Author(s):  
B D Lemon ◽  
J D Fondell ◽  
L P Freedman
Keyword(s):  
Target Genes ◽  
Nuclear Hormone Receptor ◽  
Mobility Shift ◽  
Dihydroxyvitamin D3 ◽  
Transcription System ◽  
1,25 Dihydroxyvitamin D3 ◽  
Nuclear Extracts ◽  
Heterodimeric Complex ◽  
Gel Mobility Shift

The numerous members of the steroid/nuclear hormone receptor superfamily act as direct transducers of circulating signals, such as steroids, thyroid hormone, and vitamin or lipid metabolites, and modulate the transcription of specific target genes, primarily as dimeric complexes. The receptors for 9-cis retinoic acid and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], RXR and VDR, respectively, as members of this superfamily, form a heterodimeric complex and bind cooperatively to vitamin D responsive elements (VDREs) to activate or repress the transcription of a multitude of genes which regulate a variety of physiological functions. To directly investigate RXR- and VDR-mediated transactivation, we developed a cell-free transcription system for 1,25(OH)2D3 signaling by utilizing crude nuclear extracts and a G-free cassette-based assay. Transcriptional enhancement in vitro was dependent on purified, exogenous RXR and VDR and was responsive to physiological concentrations of 1,25(OH)2D3. We found that RXR and VDR transactivated selectively from VDRE-linked templates exclusively as a heterodimeric complex, since neither receptor alone enhanced transcription in vitro. By the addition of low concentrations of the anionic detergent Sarkosyl to limit cell-free transcription to a single round and the use of agarose gel mobility shift experiments to assay factor complex assembly, we observed that 1,25(OH)2D3 enhanced RXR:VDR-mediated stabilization or assembly of preinitiation complexes to effect transcriptional enhancement from VDRE-linked promoter-containing DNA.

scholarly journals Semaphorin 3B Is a 1,25-Dihydroxyvitamin D3-Induced Gene in Osteoblasts that Promotes Osteoclastogenesis and Induces Osteopenia in Mice

2008 ◽  
Vol 22 (6) ◽  
pp. 1370-1381 ◽  
Author(s):  
Amelia L. M. Sutton ◽  
Xiaoxue Zhang ◽  
Diane R. Dowd ◽  
Yogendra P. Kharode ◽  
Barry S. Komm ◽  
...  
Keyword(s):  
Target Genes ◽  
Biological Effects ◽  
Osteoblastic Cells ◽  
Northern Analysis ◽  
Mineral Density ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Skeletal Homeostasis

Abstract The vitamin D endocrine system is important for skeletal homeostasis. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] impacts bone indirectly by promoting intestinal absorption of calcium and phosphate and directly by acting on osteoblasts and osteoclasts. Despite the direct actions of 1,25(OH)2D3 in bone, relatively little is known of the mechanisms or target genes that are regulated by 1,25(OH)2D3 in skeletal cells. Here, we identify semaphorin 3B (SEMA3B) as a 1,25(OH)2D3-stimulated gene in osteoblastic cells. Northern analysis revealed strong induction of SEMA3B mRNA by 1,25(OH)2D3 in MG-63, ST-2, MC3T3, and primary osteoblastic cells. Moreover, differentiation of these osteogenic cells enhanced SEMA3B gene expression. Biological effects of SEMA3B in the skeletal system have not been reported. Here, we show that osteoblast-derived SEMA3B alters global skeletal homeostasis in intact animals and osteoblast function in cell culture. Osteoblast-targeted expression of SEMA3B in mice resulted in reduced bone mineral density and aberrant trabecular structure compared with nontransgenic littermates. Histomorphometry studies indicated that this was likely due to increased osteoclast numbers and activity. Indeed, primary osteoblasts obtained from SEMA3B transgenic mice stimulated osteoclastogenesis to a greater extent than nontransgenic osteoblasts. This study establishes that SEMA3B is a 1,25(OH)2D3-induced gene in osteoblasts and that osteoblast-derived SEMA3B impacts skeletal biology in vitro and in vivo. Collectively, these studies support a putative role for SEMA3B as an osteoblast protein that regulates bone mass and skeletal homeostasis.

scholarly journals Characterization of the Condensin Component Cnap1 and Protein Kinase Melk as Novel E2F Target Genes Down-regulated by 1,25-Dihydroxyvitamin D3

2005 ◽  
Vol 280 (45) ◽  
pp. 37319-37330 ◽  
Author(s):  
Lieve Verlinden ◽  
Guy Eelen ◽  
Ine Beullens ◽  
Mark Van Camp ◽  
Paul Van Hummelen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Target Genes ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3

The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic responses in dolphin skin cells

2010 ◽  
Vol 391 (2/3) ◽  
Author(s):  
Blake C. Ellis ◽  
Sebastiano Gattoni-Celli ◽  
Mark S. Kindy
Keyword(s):  
Vitamin D ◽  
Target Genes ◽  
Protective Role ◽  
Dihydroxyvitamin D3 ◽  
Skin Cells ◽  
1,25 Dihydroxyvitamin D3 ◽  
Atlantic Bottlenose Dolphin ◽  
Considerable Impact ◽  
The Impact

Abstract The Atlantic bottlenose dolphin has been the focus of much attention owing to the considerable impact of environmental stress on its health and the associated implications for human health. Here, we used skin cells from the dolphin to investigate the protective role of the vitamin D pathway against environmental stressors. We previously reported that dolphin skin cells respond to 1,25-dihydroxyvitamin D3 (1,25D3), the bioactive metabolite of vitamin D3, by upregulation of the vitamin D receptor (VDR) and expression of several genes. Methylmercury is a highly bioaccumulative environmental stressor of relevance to the dolphin. We currently report that in dolphin cells sublethal concentrations of methylmercury compromise the ability of 1,25D3 to upregulate VDR, to transactivate a vitamin D-sensitive promoter, and to express specific target genes. These results help elucidate the effects of vitamin D and methylmercury on innate immunity in dolphin skin and potentially in human skin as well, considering similarities in the vitamin D pathway between the two species.

scholarly journals Genomic mechanisms involved in the pleiotropic actions of 1,25-dihydroxyvitamin D3

1996 ◽  
Vol 316 (2) ◽  
pp. 361-371 ◽  
Author(s):  
Sylvia CHRISTAKOS ◽  
Mihali RAVAL-PANDYA ◽  
Roman P. WERNYJ ◽  
Wen YANG
Keyword(s):  
Vitamin D ◽  
Transcription Factor ◽  
Target Genes ◽  
Hormone Secretion ◽  
Biologically Active ◽  
Receptor Protein ◽  
Future Research ◽  
Dihydroxyvitamin D3 ◽  
Inhibition Of Proliferation ◽  
1,25 Dihydroxyvitamin D3

The biologically active metabolite of vitamin D (cholecalciferol), i.e. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a secosteroid hormone whose mode of action involves stereospecific interaction with an intracellular receptor protein (vitamin D receptor; VDR). 1,25(OH)2D3 is known to be a principal regulator of calcium homeostasis, and it has numerous other physiological functions including inhibition of proliferation of cancer cells, effects on hormone secretion and suppression of T-cell proliferation and cytokine production. Although the exact mechanisms involved in mediating many of the different effects of 1,25(OH)2D3 are not completely defined, genomic actions involving the VDR are clearly of major importance. Similar to other steroid receptors, the VDR is phosphorylated; however, the exact functional role of the phosphorylation of the VDR remains to be determined. The VDR has been reported to be regulated by 1,25(OH)2D3 and also by activation of protein kinases A and C, suggesting co-operativity between signal transduction pathways and 1,25(OH)2D3 action. The VDR binds to vitamin D-responsive elements (VDREs) in the 5´ flanking region of target genes. It has been suggested that VDR homodimerization can occur upon binding to certain VDREs but that the VDR/retinoid X receptor (RXR) heterodimer is the functional transactivating species. Other factors reported to be involved in VDR-mediated transcription include chicken ovalbumin upstream promoter (COUP) transcription factor, which is involved in active silencing of transcription, and transcription factor IIB, which has been suggested to play a major role following VDR/RXR heterodimerization. Newly identified vitamin D-dependent target genes include those for Ca2+/Mg2+-ATPase in the intestine and p21 in the myelomonocytic U937 cell line. Elucidation of the mechanisms involved in the multiple actions of 1,25(OH)2D3 will be an active area of future research.

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