Gene Expression Regulation by Vitamin D Receptor Pathway

Preferred Label : Gene Expression Regulation by Vitamin D Receptor Pathway;

NCIt related terms : Control of Gene Expression by Vitamin D Receptor;

NCIt definition : A pathway that modulates the expression of genes involved in calcium homeostasis, bone formation, cellular differentiation, cell growth and apoptosis through the direct interaction between the nuclear receptor, vitamin D3 receptor (VDR), primarily as part of a heterodimeric complex with the retinoid X receptor (RXR), and vitamin D response elements (VDREs) found in the promoter regions of vitamin D regulated genes.;

Alternative definition : BIOCARTA: The vitamin D receptor, VDR is the mediator of all genomic actions of vitamin D3 and its analogs. It belongs to a family of ligand induced transcription factors, nuclear receptors (NRs). Vitamin D3 is the main regulator of calcium homeostasis and is critical in bone formation. It is also involved in controlling cellular growth, differentiation, and apoptosis, which makes synthetic vitamin D3 analogues interesting for therapy of such diseases as cancer and psoriasis. NRs are comprised of an amino-terminal activation function domain AF-1, the DNA-binding domain, a hinge region, and a carboxy-terminal ligand-binding domain containing a second activation function, AF-2. VDR acts primarily as a heterodimer with the retinoid X receptor (RXR) on vitamin D response elements (VDREs). It interacts with the transcription machinery and nuclear receptor coactivators or corepressors to regulate target gene activity. NR's coregulators can be divided into 3 major classes: 1) ATP-dependent chromatin remodeling complexes that are involved in the location and association of nucleosomes with DNA; 2) Enzymes that catalyze modifications of histone tails to regulate histone-histone and histone-DNA interactions; 3) General transcription factor adaptors that bridge the functions between regulators and basal transcription factors. A novel multifunctional ATP-dependent chromatin remodeling complex, WINAC, directly interacts with the vitamin D receptor. It contains BRG1 or hBRM as ATPase subunits as all SWI/SNF complexes do, but it also has subunits associated with DNA replication (TopoII and CAF-1p150) and transcript elongation through nucleosomes (FACTP140) not found before in SWI/SNF complexes. WINAC also contains the Williams syndrome transcription factor (WSTF). WSTF appears to function as a platform protein for the assembly of components in WINAC, and it interacts directly with the vitamin D receptor in a ligand-independent manner. WINAC and vitamin D receptor are targeted to vitamin D responsive promoters in the absence of ligand to both positively and negatively regulated genes. WINAC may rearrange the nucleosome array around the positive and negative VDREs, thereby facilitating the coregulatory complex's access for further transcription control. Upon ligand binding, two HAT complexes, p160/CBP and TRRAP/PCAF, coactivate the NR function. The p160 proteins (SRC protein family) interact directly with an NR activation surface AF2 and serve as platforms for the recruitment of histone-modifying enzymes, including CBP/p300 and methyltransferases. The SRC/p160 family members SRC-1 and p/CIP, as well as CBP and p300 contain intrinsic histone acetyltransferase activity (HAT). Both the HAT activity and the histone methyltransferase activity may cooperate in histone modification and facilitate nucleosome remodeling and recruitment of transcriptional machinery. A third group of coactivators is represented by thyroid receptor-associated proteins (TRAP)/vitamin D receptor-interacting proteins (DRIP). This complex may play a role by directly contacting the basal transcriptional machinery. As the VDR/RXR heterodimer also represses transcription in a ligand-dependent manner through negative VDRE (nVDRE), a number of corepressor proteins such as NCoR and ALIEN may also be recruited to the surface of the receptor. They, too, function as platforms but serve to recruit enzymes such as histone deacetylases. WINAC association with VDR facilitates targeting of a putative corepressor complex to the nVDRE. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_vdrPathway;

Details

Origin ID

C39263;

UMLS CUI

C1517487;

Semantic type(s)
- Genetic Function [UMLS semantic type]
has_gene_product_element
- AT-Rich Interactive Domain-Containing Protein 1A [NCIt concept]
- CREB-Binding Protein [NCIt concept]
- Chromatin Assembly Factor 1 Subunit A [NCIt concept]
- DNA Topoisomerase 2-Beta [NCIt concept]
- Histone Acetyltransferase KAT2B [NCIt concept]
- Histone Acetyltransferase p300 [NCIt concept]
- Histone Deacetylase 1 [NCIt concept]
- Histone-Arginine Methyltransferase CARM1 [NCIt concept]
- Mediator of RNA Polymerase II Transcription Subunit 1 [NCIt concept]
- Nuclear Receptor Coactivator 1 [NCIt concept]
- Nuclear Receptor Coactivator 2 [NCIt concept]
- Nuclear Receptor Coactivator 3 [NCIt concept]
- Nuclear Receptor Corepressor 1 [NCIt concept]
- Protein Arginine N-Methyltransferase 1 [NCIt concept]
- Retinoic Acid Receptor RXR-Alpha [NCIt concept]
- SNW Domain-Containing Protein 1 [NCIt concept]
- SWI/SNF Complex Subunit SMARCC1 [NCIt concept]
- SWI/SNF Complex Subunit SMARCC2 [NCIt concept]
- SWI/SNF-Related Matrix-Associated Actin-Dependent Regulator of Chromatin Subfamily D Member 1 [NCIt concept]
- SWI/SNF-Related Matrix-Associated Actin-Dependent Regulator of Chromatin Subfamily E Member 1 [NCIt concept]
- Transcription Activator BRG1 [NCIt concept]
- Tuberin [NCIt concept]
- Vitamin D3 Receptor [NCIt concept]
pathway_has_gene_element
- ARID1A wt Allele [NCIt concept]
- CARM1 wt Allele [NCIt concept]
- CHAF1A wt Allele [NCIt concept]
- CREBBP wt Allele [NCIt concept]
- EP300 wt Allele [NCIt concept]
- HDAC1 wt Allele [NCIt concept]
- KAT2B wt Allele [NCIt concept]
- MED1 wt Allele [NCIt concept]
- NCOA1 wt Allele [NCIt concept]
- NCOA2 wt Allele [NCIt concept]
- NCOA3 wt Allele [NCIt concept]
- NCOR1 wt Allele [NCIt concept]
- PRMT1 wt Allele [NCIt concept]
- RXRA wt Allele [NCIt concept]
- SMARCA4 wt Allele [NCIt concept]
- SMARCC1 wt Allele [NCIt concept]
- SMARCC2 wt Allele [NCIt concept]
- SMARCD1 wt Allele [NCIt concept]
- SMARCE1 wt Allele [NCIt concept]
- SNW1 wt Allele [NCIt concept]
- TOP2B wt Allele [NCIt concept]
- TSC2 wt Allele [NCIt concept]
- VDR wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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