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At least 253 records · Page 14Linked to original sources
PubMed1995

Regulation of insulin-like growth factor I transcription by cyclic adenosine 3',5'-monophosphate (cAMP) in fetal rat bone cells through an element within exon 1: protein kinase A-dependent control without a consensus AMP response element.

Insulin-like growth factor I (IGF-I) is a locally synthesized anabolic growth factor for bone. IGF-I synthesis by primary fetal rat osteoblasts (Ob) is stimulated by agents that increase the intracellular cAMP concentration, including prostaglandin E2 (PGE2). Previous studies with Ob cultures demonstrated that PGE2 enhanced IGF-I transcription through selective use of IGF-I promoter 1, with little effect on IGF-I messenger RNA half-life. Transient transfection of Ob cultures with an array of promoter 1-luciferase reporter fusion constructs has now allowed localization of a potential cis-acting promoter element(s) responsible for cAMP-stimulated gene expression to the 5'-untranslated region (5'-UTR) of IGF-I exon 1, within a segment lacking a consensus cAMP response element. Our evidence derives from three principal observations: 1) a transfection construct containing only 122 nucleotides (nt) of promoter 1 and 328 nt of the 5'-UTR retained full PGE2-stimulated reporter expression; 2) maximal PGE2-driven reporter expression required the presence of nt 196 to 328 of exon 1 when tested within the context of IGF-I promoter 1; 3) cotransfection of IGF-I promoter-luciferase-reporter constructs with a plasmid encoding the alpha-isoform of the catalytic subunit of murine cAMP-dependent protein kinase (PKA) produced results comparable to those seen with PGE2 treatment, whereas cotransfection with a plasmid encoding a mutant regulatory subunit of PKA that cannot bind cAMP blocked PGE2-induced reporter expression. Deoxyribonuclease I footprinting of the 5'-UTR of exon 1 demonstrated protected sequences at HS3A, HS3B, and HS3D, three of six DNA-protein binding sites previously characterized with rat liver nuclear extracts. Of these three regions, only the HS3D binding site is located within the functionally identified hormonally responsive segment of IGF-I exon 1. These results directly implicate PKA in the control of IGF-I gene transcription by PGE2 and identify a segment of IGF-I exon 1 as being essential for this hormonal regulation.

Animals↗
PubMed2002

Regulation of the interferon-inducible PKR kinase gene: the KCS element is a constitutive promoter element that functions in concert with the interferon-stimulated response element.

The RNA-dependent protein kinase PKR plays important roles in the antiviral and antiproliferative actions of IFN. The IFN-inducible promoter of the human PKR gene contains a 15-bp DNA element designated KCS. The KCS element is located 4 bp upstream of the interferon-stimulated response element (ISRE) and is required for both basal and IFN-inducible transcription. We have examined the effect of insertion mutations between the KCS and the ISRE elements, as well as altered orientation of the KCS element relative to the ISRE element, to assess a possible functional interaction between them. Large insertions (>or=93 bp) between the KCS and ISRE elements significantly reduced both basal and IFN-inducible promoter activity. The function of the KCS element was dependent on the orientation of KCS relative to the ISRE element. Multimerization of the KCS element increased both basal and IFN-inducible transcription. Electrophoretic mobility shift analyses (EMSA) identified IFN-inducible protein complex formation that required both the KCS and the ISRE DNA element sequences. The novel IFN-inducible protein complexes contained the transcription factor STAT1, as shown by supershift analyses and by their presence in extracts prepared from STAT1 wild-type but not from STAT1-/- null cells. These results, taken together, strongly suggest that the KCS and ISRE elements of the human PKR promoter represent a functional unit.

Animals↗
PubMed2002

Existence of xenobiotic response element binding in Dictyostelium.

Xenobiotic response element (XRE) is a core nucleotide sequence at the upstream of inducible target genes for the transcription factor aryl hydrocarbon receptor (AhR) that is responsible for recognition of exogenous environmental pollutants in eukaryotic cells. Gel retardation electrophoresis revealed the presence of binding of a radiolabeled probe containing XRE in both cytosolic and nuclear preparations of the slime mold Dictyostelium. Unlabeled XRE probe was more potent in competing for XRE binding in both fractions than unlabeled XRE probe with a point mutation at the core element. Limited proteolysis by V8 protease did not markedly affect XRE binding in both fractions, while XRE binding decreased during in vitro incubation at 30 degrees C for up to 24 h at decline rates proportional to increasing pHs at a range of 6.5-8.5 in cytosolic fractions in a manner different from those in nuclear fractions. Deprivation of nutrients induced aggregation of cells within 4-8 h later, followed by formation of first finger tips around 12 h later and subsequent development to mobile slugs within 16 h and then to fruit bodies between 20 and 24 h later. The starvation led to a marked decrement of XRE binding in cytosolic fractions 4-36 h later, followed by a robust but transient increment of that in nuclear extracts 12-20 h afterward. However, XRE binding was not affected by antibodies against AhR-related proteins known to date in both fractions irrespective of nutritional conditions. These results suggest the abundance of as-yet unidentified proteins with high affinity for XRE in the slime mold Dictyostelium. The possibility that those proteins may be translocated from the cytoplasm to the nucleus in response to cellular development during starvation is feasible.

Animals↗
PubMed1995

Natural vitamin D3 response elements formed by inverted palindromes: polarity-directed ligand sensitivity of vitamin D3 receptor-retinoid X receptor heterodimer-mediated transactivation.

VDR, the nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), is a member of the superfamily of nuclear hormone receptors and controls multiple aspects of homeostasis, cell growth, and differentiation. VDR can function as a homodimer, but heterodimerization with the retinoid X receptor (RXR), retinoic acid receptor, or thyroid hormone receptor increases its affinity for response elements in the promoter of target genes. All natural VD response elements identified so far consist of direct repeats of a variety of hexameric core binding motifs with a preferential spacing of three nucleotides (DR3s). However, all four VD signalling pathways function also on response elements formed by inverted palindromes, although these sequences were not of natural origin. Here, we report the identification of two VD response elements consisting of inverted palindromes spaced by nine nucleotides (IP9s) in the promoters of the human calbindin D9k gene and the rat osteocalcin gene. Like most DR3-type VD response elements, both IP9s are preferentially bound by VDR-RXR heterodimers with a 5'-RXR-VDR-3' polarity, whose transcriptional activity can be enhanced by costimulation with 9-cis retinoic acid. We demonstrate that changing the response element orientation relatively to the basal promoter decreases the sensitivity of transcriptional activation by VD by about 10-fold. Our findings indicate that inverted palindromes are as functional as direct repeats. Furthermore, we suggest that the orientation of a nuclear receptor complex in relation to the basic transcriptional machinery, which is directed by heterodimer polarity and response element orientation, influences the ligand sensitivity of the respective target gene expression.

Animals↗
PubMed1997

Identification and characterization of a novel androgen response element composed of a direct repeat.

Transcriptional regulation by the androgen receptor (AR) requires its binding to hormone response element nucleotide sequences in DNA. A consensus glucocorticoid response element (GRE) can mediate transactivation by AR and other members of the AR/glucocorticoid (GR)/progesterone (PR)/mineralocorticoid (MR) receptor subfamily. We identified putative androgen response element (ARE) sequences by binding of a human AR DNA-binding domain fusion protein to DNA in a random sequence selection assay. A 17-base pair consensus nucleotide sequence, termed IDR17, containing three potential GRE-like core binding sites organized as both inverted and direct repeats, was determined from a pool of degenerate oligonucleotides. IDR17 was active in mediating androgen-dependent induction of reporter gene expression in transient transfection assays. Dissection of the IDR17 sequence revealed an 11-base pair sequence (DR-1), consisting of two potential core binding sites oriented as an overlapping direct repeat, as the most potent ARE. DR-1 demonstrated a strong preference for AR binding and transactivation when compared with GR. To our knowledge, this is the first observation that a direct repeat of GRE-like core motifs functions as a preferred hormone response element within the AR/GR/PR/MR subfamily of nuclear receptors.

Base Sequence↗
PubMed2000

Oestrogen receptor function at classical and alternative response elements.

The oestrogen receptor (ER), bound to classical response elements (EREs) in the promoter of target genes, activates transcription by recruiting coactivator proteins. We will describe structural studies that show that oestrogens allow the formation of a hydrophobic cleft on the surface of the ER that serves as a docking site for coactivators. Anti-oestrogens displace part of the receptor, which then occludes the site, blocking coactivator access. In addition to activating at classical EREs, the ER activates transcription at alternative elements such as AP-1 sites. These bind the Jun/Fos proteins but not ER. Interestingly both oestrogen and tamoxifen activate transcription at AP-1 sites. We propose a mechanism whereby oestrogen and anti-oestrogen allow ER to activate transcription from alternative response elements. ER binds to the coactivators, CBP and GRIP1, that have been recruited by Jun/Fos and through this contact 'triggers' these coactivators into full activity. In this circumstance the ER is part of the coactivator complex for Jun/Fos.

Animals↗
PubMed1998

A proximal element within the human alpha 2(I) collagen (COL1A2) promoter, distinct from the tumor necrosis factor-alpha response element, mediates transcriptional repression by interferon-gamma.

Previous studies have shown that interferon-gamma (IFN-gamma) inhibits type I collagen gene expression through both transcriptional and post-transcriptional mechanisms (Kahäri et al., 1990). In the present study, using transient cell transfections of human dermal fibroblast cultures with a series of 5' deletion promoter/CAT reporter gene constructs, we have identified the IFN-gamma-response element of the human alpha 2(I) collagen gene (COL1A2) promoter. Specifically, we have identified a segment of the proximal promoter region, located between nucleotides -161 and -125 relative to the transcription start site, as critical for down-regulation of COL1A2 promoter activity by IFN-gamma. This IFN-gamma response element (IgRE) is clearly distinct from the previously described tumor necrosis factor-alpha response element (TaRE) located between nucleotides -265 and -241 of the COL1A2 promoter, a difference which is likely to explain the additive inhibitory effect of these two cytokines. The inhibitory effect of IFN-gamma was dose-dependent and rapidly induced, requiring less than 5 min exposure of fibroblast cultures. Gel mobility shift assays indicated that a highly specific nuclear protein complex bound to this 37-base pair region of promoter. Competition experiments with oligonucleotides spanning discrete segments of this promoter region mapped the binding element within a distinctive pyrimidine-rich sequence. Point mutations within the latter revealed that this element plays a crucial role not only in the IFN-gamma response, but also in the basal activity of the proximal promoter. Substitution mutations within the IgRE of the -161/CAT construct attenuated the promoter response to IFN-gamma, as measured in transient cell transfections, and eliminated specific DNA/protein complex formation, as measured by gel mobility shift assay. UV-crosslinking experiments indicated that two DNA/protein complexes were formed with the IgRE, with molecular weights around 55 kDa and 30 kDa, corresponding to proteins of approximately 30 kDa and approximately 6 kDa, respectively. Our results further clarify the molecular mechanisms involved in the regulation of type I collagen gene expression by IFN-gamma.

Binding, Competitive↗
PubMed1994

Half-site arrangement of hybrid glucocorticoid and thyroid hormone response elements specifies thyroid hormone receptor complex binding to DNA and transcriptional activity.

Thyroid hormone receptors bind to thyroid hormone response elements (TREs) as heterodimers with 3,5,3'-L-triiodothyronine (T3) receptor auxiliary protein (TRAP) and retinoid X receptors (RXRs). Currently, it is not known whether TR/TRAP or TR/RXR heterodimers need to bind to both TRE half-sites and whether there is a preferred orientation for TR/RXR heterodimer binding to TREs or transcriptional activation. Accordingly, we created a mutant TR alpha (TR-P box) by changing 3 amino acids in the P box region of the first zinc finger of the DNA-binding domain to that of the glucocorticoid receptor (GR), and we examined wild-type TR alpha and TR-P box complex binding to hybrid response elements containing TRE and glucocorticoid receptor element (GRE) half-sites arranged as a direct repeat with a four-nucleotide gap. TR-P box/RXR heterodimers selectively bound to the hybrid response elements in which GRE half-site was the downstream half-site, whereas TR alpha/RXR bound to hybrid response elements in which GREs were in either position. Additionally, TR/TRAP or TR/RXR heterodimer required two half-sites for binding to DNA, with strong binding to at least one of the half-sites. Last, co-transfection assays and methylation interference studies using the hybrid response elements suggest that the sequential arrangement of strong and weak half-sites in the TRE may be a critical determinant of TR/RXR heterodimer binding and transcriptional activation.

Base Sequence↗
PubMed1991

A retinoic acid-responsive element in the apolipoprotein AI gene distinguishes between two different retinoic acid response pathways.

The gene coding for apolipoprotein AI, a plasma protein involved in the transport of cholesterol and other lipids in the plasma, is expressed predominantly in liver and intestine. Previous work in our laboratory has shown that hepatocyte-specific expression is determined by synergistic interactions between transcription factors bound to three separate sites, sites A (-214 to -192), B (-169 to -146), and C (-134 to -119), within a powerful liver-specific enhancer located in the region -222 to -110 nucleotides upstream of the apolipoprotein AI gene transcription start site (+1). In this study, it was found that site A is a highly selective retinoic acid-responsive element (RARE) that responds preferentially to the recently identified retinoic acid receptor RXR alpha over the previously characterized retinoic acid receptors RAR alpha and RAR beta. Control experiments indicated that a RARE in the regulatory region of the laminin B1 gene responds preferentially to RAR alpha and RAR beta over RXR alpha, while a previously described palindromic thyroid hormone-responsive element responds similarly to all three of these receptors. Gel retardation experiments showed that the activity of these RAREs is concordant with receptor binding. These results indicate that different RAREs may play a fundamental role in defining distinctive retinoic acid cellular response pathways and suggest that retinoic acid response pathways mediated by RXR alpha play an important role in cholesterol and retinoid transport and metabolism.

Adult↗
PubMed1988

Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus.

We have characterized steroid response elements in mouse mammary tumour virus (MMTV) by transient transfection. Four partial inverted repeats of the sequence TGTTCT function as response elements for androgen, as well as for glucocorticoid and progestins, although the relative hormone inductions mediated by each oligonucleotide were different. Mutational analysis of the left half of the palindrome showed that a perfect dyad symmetry is not required for optimum activity as a steroid response element. To investigate potential interactions between steroid receptors and transcription factors we have analysed the minimum sequence requirements for a hormone response. Interestingly, a single 15 bp steroid response element and a TATA box are sufficient for steroid inductions. When the distance between the two elements was increased by up to two turns of the helix the hormone induction initially increased and then gradually declined with no obvious periodicity.

Animals↗
PubMed2005

Transcriptional co-operativity between distant retinoic acid response elements in regulation of Cyp26A1 inducibility.

Cyp26A1 encodes an RA (retinoic acid)-catabolizing CYP (cytochrome P450) protein that plays a critical role in regulating RA distribution in vivo. Cyp26A1 expression is inducible by RA, and the locus has previously been shown to contain a RARE (RA response element), R1, within the minimal promoter [Loudig, Babichuk, White, Abu-Abed, Mueller and Petkovich (2000) Mol. Endocrinol. 14, 1483-1497]. In the present study, we report the identification of a second functional RARE (R2) located 2.0 kb upstream of the Cyp26A1 transcriptional start site. Constructs containing murine sequences encompassing both R1 and R2 showed that these elements work together to generate higher transcriptional activity upon treatment with RA than those containing R1 alone. Inclusion of R2 also dramatically enhanced the sensitivity of reporter constructs to RA, as even treatment with 10(-8) M RA resulted in a 5-fold induction of reporter activity. Mutational analysis identified R2 as the functional element responsible for the increased RA inducibility of promoter constructs. The element was shown to bind RARgamma (RA receptor gamma)/RXRalpha (retinoid X receptor alpha) heterodimers in vitro, and inclusion of nuclear receptors in transfections boosted the transcriptional response. A construct containing both R1 and R2 was used to generate a stable luciferase reporter cell line that can be used as a tool to identify factors regulating Cyp26A1 expression. The analysis of R1 and R2 has led to the proposal that the two elements work synergistically to provide a maximal response to RA and that R2 is an upstream enhancer.

Animals↗
PubMed2004

Identification of a functional serum response element in the HTLV-I LTR.

In response to various mitogenic signals, serum response factor (SRF) activates cellular gene expression after binding to its cognate target sequence (CArG box) located within a serum response element (SRE). SRF is particularly important in T cell activation, and we now report that SRF activates basal transcription from the human T-cell leukemia virus-I (HTLV-I) long terminal repeat (LTR). A DNA element, with similarity to the consensus cellular CArG box found in the c-fos promoter centered approximately 120 base pairs upstream from the viral transcription start site, has been identified and named the vCArG box. SRF activation of gene expression from the LTR was localized to the vCArG box, and mutation of this site abolished SRF responsiveness. An oligonucleotide probe containing the vCArG box bound purified SRF, and a complex formed on this probe with nuclear extract was supershifted by anti-SRF antibody. Moreover, a biotinylated probe containing the vCArG box bound SRF in avidin-biotin pull-down assays. Quantitative binding analysis yielded nanomolar affinities for both the viral and cellular CArG boxes. Chromatin immunoprecipitation experiments demonstrated that SRF is resident on the HTLV-I LTR in vivo. These data identify a functional serum response element in the HTLV-I LTR and suggest that SRF may play an important role in regulating basal HTLV-I gene expression in early infection and reactivation from latency.

Base Sequence↗
PubMed1996

Function of directly repeated half-sites as response elements for steroid hormone receptors.

The mouse mammary tumor virus promoter has been shown to be inducible by glucocorticoids and progesterone. Although steroid hormone receptors bind with high affinity to palindromic response elements, the hormone-responsive region of the mouse mammary tumor virus promoter contains a pair of directly repeated half-sites that are important for hormone inducibility. Recent experiments have also indicated that direct repeats can function as estrogen response elements. Here, we have investigated DNA binding by steroid receptors to direct repeats and provide evidence using gel retardation assays, methylation interference, and gene transfer experiments that direct repeats of TGTTCT or RGGTCA motifs function as response elements for glucocorticoid (GR) or estrogen receptors (ER), respectively, by binding receptor homodimers. Specific GR- or ER-DNA complexes were observed on direct repeats with different spacings between half-sites, indicating that binding of steroid receptors to direct repeats is more flexible than binding to palindromic elements. This flexibility was further emphasized by the observation that the GR could also bind to everted repeats of TGTTCT motifs separated by 9 base pairs. The isolated DNA binding domains of the GR and ER bound cooperatively to palindromes, but no evidence was observed for cooperative binding to direct repeats. Under similar conditions the DNA binding domains of retinoid receptors retinoid X receptor and retinoic acid receptor bound to direct repeats cooperatively as heterodimers. Similarly, ER derivative HE15, which lacks a functional ligand binding domain, bound palindromic response elements but failed to bind direct repeats. These results indicate that the dimerization domain in the ligand binding domain is essential for binding of steroid receptors to direct repeats and that the dimerization domain in the D-box of the DNA binding is not functional under these conditions. Moreover, the results suggest that steroid receptor DNA binding domains may lack dimerization domains outside the D-box, which would function in binding to direct repeats, in contrast to receptors for retinoids and thyroid hormone. A comparison of the mechanisms of binding of steroid receptors and retinoid and thyroid hormone receptors to direct repeats is presented.

Animals↗
PubMed1994

3,5,3'-L-triiodothyronine (thyroid hormone)-induced protein-DNA interactions in the thyroid hormone response elements and cell type-specific elements of the rat growth hormone gene revealed by in vivo dimethyl sulfate footprinting.

The cell type-specific element and 3,5,3'-L-triiodothyronine (thyroid hormone) (T3) response element of the rat growth hormone gene act synergistically to produce cell type-specific, T3-regulated expression. Pit-1 is a pituitary cell type-specific transcription factor that binds the cell type-specific element and is essential to its activity. T3 receptors bind as homodimers and heterodimers to the T3 response element and are essential for its activity. Here, we report the use of ligation-mediated polymerase chain reaction in vivo dimethyl sulfate footprinting to study the effects of T3 on protein-DNA interactions in the rat growth hormone gene promoter in vivo. T3-responsive guanine methylation was detected only in and near the T3 response element and the Pit-1 binding sites. The results indicate that within 2 h, T3 induces occupancy of the T3 response element and Pit-1 sites by their respective trans-acting factors in vivo.

Animals↗
PubMed1999

Autonomously binding protein detected on ets box of c-fos serum response element in proliferating cells.

The serum response element (SRE) in the c-fos promoter contains an ets box whose integrity is required for full activation of this proto-oncogene by nerve growth factor (NGF) in PC12 rat pheochromocytoma cells. Electrophoretic mobility shift assays (EMSA) detect a protein in nuclear extracts that binds to the wild-type SRE, but not to an SRE containing a mutated ets box. Competition studies using unlabeled probes, and supershift experiments using antibodies and in vitro translated core serum response factor (SRF) indicate that the protein in question is not YY1, SAP-1, nor Elk-1 and that it does not exhibit ternary complex factor (TCF) activity, so that it may correspond to an autonomously binding Ets family protein. The complete disappearance of this "Ets-like autonomous binding factor" upon terminal differentiation of both L6alpha2 myoblastic and PC12 pheochromocytoma cells points to a possible role in the proliferation/differentiation process.

3T3 Cells↗
PubMed1993

Recombinant iron-regulatory factor functions as an iron-responsive-element-binding protein, a translational repressor and an aconitase. A functional assay for translational repression and direct demonstration of the iron switch.

The translation of ferritin and erythroid 5-aminolevulinate synthase mRNAs is regulated via a specific high-affinity interaction between an iron-responsive element in the 5' untranslated region of ferritin and erythroid 5-aminolevulinate synthase mRNAs and a 98-kDa cytoplasmic protein, the iron-regulatory factor. Iron-regulatory factor was expressed in vaccinia-virus-infected HeLa cells (hIRFvac) and in Escherichia coli (hIRFeco). An N-terminal histidine tag allowed a rapid one-step purification of large quantities of soluble recombinant protein. Both hIRFvac and hIRFeco bound specifically to iron-responsive elements and were immunoprecipitated by iron-regulatory-factor antibodies. Using in-vitro-transcribed chloramphenicol-acetyltransferase mRNAs bearing an iron-responsive element in the 5' untranslated region, specific repression of chloramphenicol-acetyltransferase translation by hIRFvac and hIRFeco was demonstrated in wheat-germ extract. In addition, hIRFvac and hIRFeco were shown to display aconitase activity. Treatment of hIRFvac and hIRFeco with FeSO4 resulted in a drastic reduction in iron-responsive-element-binding of iron-regulatory factor, but caused a strong stimulation of its aconitase activity. The results establish that recombinant iron-regulatory factor is a bifunctional protein; after purification, it binds to iron-responsive elements and represses translation in vitro. Following iron treatment, iron-responsive-element binding is lost and aconitase activity is gained. No eukaryotic co-factor seems to be required for the conversion of the iron-responsive-element binding to the aconitase form of the protein.

Aconitate Hydratase↗
PubMed2002

Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D.

The calcium-sensing receptor (CASR), expressed in parathyroid chief cells, thyroid C-cells, and cells of the kidney tubule, is essential for maintenance of calcium homeostasis. Here we show parathyroid, thyroid, and kidney CASR mRNA levels increased 2-fold at 15 h after intraperitoneal injection of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in rats. Human thyroid C-cell (TT) and kidney proximal tubule cell (HKC) CASR gene transcription increased approximately 2-fold at 8 and 12 h after 1,25(OH)2D3 treatment. The human CASR gene has two promoters yielding alternative transcripts containing either exon 1A or exon 1B 5'-untranslated region sequences that splice to exon 2 some 242 bp before the ATG translation start site. Transcriptional start sites were identified in parathyroid gland and TT cells; that for promoter P1 lies 27 bp downstream of a TATA box, whereas that for promoter P2, which lacks a TATA box, lies in a GC-rich region. In HKC cells, transcriptional activity of a P1 reporter gene construct was 11-fold and of P2 was 33-fold above basal levels. 10(-8) m 1,25(OH)2D3 stimulated P1 activity 2-fold and P2 activity 2.5-fold. Vitamin D response elements (VDREs), in which half-sites (6 bp) are separated by three nucleotides, were identified in both promoters and shown to confer 1,25(OH)2D3 responsiveness to a heterologous promoter. This responsiveness was lost when the VDREs were mutated. In electrophoretic mobility shift assays with either in vitro transcribed/translated vitamin D receptor and retinoid X receptor-alpha, or HKC nuclear extract, specific protein-DNA complexes were formed in the presence of 1,25(OH)2D3 on oligonucleotides representing the P1 and P2 VDREs. In summary, functional VDREs have been identified in the CASR gene and provide the mechanism whereby 1,25(OH)2D up-regulates parathyroid, thyroid C-cell, and kidney CASR expression.

Alternative Splicing↗
PubMed1990

Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene.

We present evidence that the vitamin D response element in the human osteocalcin gene confers responsiveness to the vitamin A metabolite, retinoic acid. Retinoic acid receptor (RAR) expressed in E. coli binds to this sequence in vitro. Transfection of RAR expression vectors in cultured cells activates heterologous promoters containing this sequence in vivo. This response element contains a consensus AP-1 site TGACTCA and in vitro is bound by the Jun-Fos complex. Unexpectedly, cotransfection of Jun and Fos expression vectors suppresses basal level transcription of the osteocalcin gene and suppresses induction by both retinoic acid and vitamin D3. Additional studies delimit an 11 nucleotide segment as a minimal hormone response element containing the AP-1 site as its core. These results indicate that two distinct classes of transcription factors can recognize common regulatory sequences, a phenomenon we refer to as cross-coupling.

Animals↗