Novel Target Genes of RUNX2 Transcription Factor and 1,25-Dihydroxyvitamin D3

2014 ◽  
Vol 115 (9) ◽  
pp. 1594-1608 ◽  
Author(s):  
Alexandre S. Stephens ◽  
Nigel A. Morrison
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Novel Target

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.

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 Identification of Novel Target Genes of the Bone-Specific Transcription Factor Runx2

2004 ◽  
Vol 19 (6) ◽  
pp. 959-972 ◽  
Author(s):  
Michael Stock ◽  
Henning Schäfer ◽  
Manfred Fliegauf ◽  
Florian Otto
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Specific Transcription Factor ◽  
Novel Target

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 Cellular Expression Levels of the Vitamin D Receptor Are Critical to Its Transcriptional Regulation by the Pituitary Transcription Factor Pit-1

2007 ◽  
Vol 21 (7) ◽  
pp. 1513-1525 ◽  
Author(s):  
Samuel Seoane ◽  
Isabel Ben ◽  
Viviana Centeno ◽  
Roman Perez-Fernandez
Keyword(s):  
Vitamin D ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Vitamin D Receptor ◽  
Binding Protein ◽  
Target Cells ◽  
Dihydroxyvitamin D3 ◽  
Expression Levels ◽  
1,25 Dihydroxyvitamin D3 ◽  
Mcf 7

Abstract The biological role of 1,25-dihydroxyvitamin D3 has generally been related to calcium homeostasis, but this hormone also has fundamental effects on processes of cellular proliferation and differentiation. The genomic actions of 1,25-dihydroxyvitamin D3 are mediated by the vitamin D receptor (VDR) present in target cells. However, VDR transcriptional regulation is not well understood, probably attributable to the complexity of the VDR gene and its promoter. In the present study, it is demonstrated that administration of the pituitary transcription factor Pit-1 (originally found in the pituitary gland but also present in other nonpituitary cell types and tissues) to the MCF-7 (human breast adenocarcinoma) cell line induces a significant increase in VDR mRNA and protein levels. Conversely, Pit-1-targeted small interference RNA markedly reduced expression of VDR in MCF-7 cells. Reporter gene assays demonstrated that the effect of Pit-1 is mediated by its binding to a region located between −254 and −246 bp from the VDR transcription start site. Selective mutations of this site completely abolished VDR transcription. Chromatin immunoprecipitation analysis showed that binding of Pit-1 to the VDR promoter leads additionally to recruitment of cAMP response element-binding protein binding protein, acetylated histone H4, and RNA polymerase II. Surprisingly, Pit-1 binding also recruits VDR protein to the VDR promoter. Using several cell lines with different levels of VDR expression, it was demonstrated that up-regulation of VDR transcription by Pit-1 is dependent on the presence of VDR protein, suggesting that transcriptional expression of VDR in a given cell type is dependent on, among other factors, its own expression levels.

scholarly journals ADAMTS-1: a novel target gene of an estrogen-induced transcription factor, EGR1, critical for embryo implantation in the mouse uterus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mira Park ◽  
So Hee Park ◽  
Hyunsun Park ◽  
Hye-Ryun Kim ◽  
Hyunjung J. Lim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Gene ◽  
Target Genes ◽  
Expression Profiles ◽  
Embryo Implantation ◽  
Uterine Epithelium ◽  
Expression Vectors ◽  
Dependent Manner ◽  
Mouse Uterus ◽  
Novel Target

Abstract Background Recently, we demonstrated that estrogen (E2) induces early growth response 1 (Egr1) to mediate its actions on the uterine epithelium by controlling progesterone receptor signaling for successful embryo implantation. EGR1 is a transcription factor that regulates the spectrum of target genes in many different tissues, including the uterus. E2-induced EGR1 regulates a set of genes involved in epithelial cell remodeling during embryo implantation in the uterus. However, only few target genes of EGR1 in the uterus have been identified. Result The expression of ADAM metallopeptidase with thrombospondin type 1 motif 1 (Adamts-1) was significantly downregulated in the uteri of E2-treated ovariectomized (OVX) Egr1(−/−) mice. Immunostaining of ADAMTS-1 revealed its exclusive expression in the uterine epithelium of OVX wild-type but not Egr1(−/−) mice treated with E2. The expression profiles of Adamts-1 and Egr1 were similar in the uteri of E2-treated OVX mice at various time points tested. Pre-treatment with ICI 182, 780, a nuclear estrogen receptor (ER) antagonist, effectively inhibited the E2-dependent induction of Egr1 and Adamts-1. Pharmacologic inhibition of E2-induced ERK1/2 or p38 phosphorylation interfered with the induction of EGR1 and ADAMTS-1. Furthermore, ADAMTS-1, as well as EGR1, was induced in stroma cells surrounding the implanting blastocyst during embryo implantation. Transient transfection with EGR1 expression vectors significantly induced the expression of ADAMTS-1. Luciferase activity of the Adamts-1 promoter containing EGR1 binding sites (EBSs) was increased by EGR1 in a dose-dependent manner, suggesting functional regulation of Adamts-1 transcription by EGR1. Site-directed mutagenesis of EBS on the Adamts-1 promoter demonstrated that EGR1 directly binds to the EBS at -1151/-1134 among four putative EBSs. Conclusions Collectively, we have demonstrated that Adamts-1 is a novel target gene of E2-ER-MAPK-EGR1, which is critical for embryo implantation in the mouse uterus during early pregnancy.

Identification of Target Genes of an Erythroid Transcription Factor Complex Containing SCL (TAL1).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4068-4068 ◽  
Author(s):  
Johanna H. Jim ◽  
Pawandeep Dhami ◽  
Amanda King ◽  
Jonathan Cooper ◽  
Dave Vetrie
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Line ◽  
K562 Cell ◽  
Target Genes ◽  
K562 Cell Line ◽  
Acute Lymphocytic Leukaemia ◽  
Novel Target ◽  
And Function ◽  
Erythroid Development

Abstract Haematopoiesis is the process whereby haematopoietic stem cells give rise to mature blood cell lineages. The SCL (TAL1) gene, originally identified by chromosomal translocations associated with T-cell acute lymphocytic leukaemia, encodes a key transcription factor (TF) which is expressed in various blood lineages and is essential for haematopoietic development. It has been shown that the SCL protein forms a multi-protein complex during erythroid development with other TFs (GATA1, E2A, LDB1, and LMO2) which binds to a sequence-specific motif to regulate the expression of glycophorin A and c-kit. We have used two complementary approaches to identify novel target genes regulated by this TF complex during erythroid development. In the first approach, we have transfected short interfering RNAs (siRNAs) into the K562 cell line to knockdown transiently the TFs of the erythroid complex. For all members of the complex, a knockdown efficiency of at least 70% was confirmed at the mRNA and protein level within 48 hours after transfection. The consequences of the knockdown at the level of gene expression were observed using Affymetrix GeneChips in order to identify downstream events associated with the erythroid complex in transcriptional programmes. In the second approach, chromatin immunoprecipitation (ChIP) was performed for each member of the complex in the K562 cell line and the ChIP material hybridised to a human transcription factor promoter microarray. A number of novel target genes for the SCL erythroid complex have been identified and verified independently using both approaches. Our data shows that members of the erythroid complex are involved in auto-regulation and regulate genes which control chromatin structure and function. These findings demonstrate that the expression of this TF complex is tightly controlled and point to an important role for it in orchestrating fundamental biological processes which have profound effects on gene expression in erythroid development.

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
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