Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Response Elements”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed2000

Induction of cAMP response element modulator (CREM) and inducible cAMP early repressor (ICER) expression in rat brain by uncompetitive N-methyl-D-aspartate receptor antagonists.

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor mediates fast excitatory neurotransmission, and agents that attenuate this function are neuroprotective, anesthetic, and psychotropic. To determine whether cAMP regulatable transcription factors play a role in the neurochemical actions of agents acting through NMDA receptors, the effects of the acute administration of uncompetitive and competitive antagonists on the expression of cAMP response element modulator (CREM) and inducible cAMP early repressor (ICER) transcription factors were examined. In situ hybridization to rat brain sections revealed that ICER mRNA expression was significantly increased by uncompetitive NMDA receptor antagonists (MK-801, phencyclidine, ketamine, memantine) but not by the competitive antagonist CPP [(+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid] or other psychotropic agents (clozapine, haloperidol, desipramine). Major brain regions where ICER transcripts were increased were the hippocampus, parietal cortex layers IV and VI, temporal cortex, cingulate cortex, thalamus, and granule cell layer of the olfactory bulb. Northern and Western blot analyses indicated that CREM mRNA and protein, respectively, were also increased after MK-801 treatment, but ICER isoforms predominate during both basal and induced conditions. MK-801 also transiently increased the binding of proteins to cAMP response element, which was supershifted by anti-CREM antibody, indicating that increased mRNA and protein levels have functional consequences on gene transcription. These results provide evidence for the involvement of CREM and ICER family transcription factors in the pharmacologic effects of uncompetitive NMDA receptor antagonists.

Animals↗
PubMed1998

Differential activation by xenoestrogens of ER alpha and ER beta when linked to different response elements.

The discovery of a second estrogen receptor (ER beta) has significant implications for our understanding of the molecular basis for the diverse actions of estrogen. Here we report the differential activation by natural and xenobiotic estrogens of ER alpha and ER beta when linked to different response elements. Receptor mediated activation of reporter constructs containing either the estrogen response element (ERE) from the vitellogenin (Vit) gene or from the luteinizing hormone beta (LH) gene were examined in transiently transfected Cos-1 cells. ER beta preferentially activated the consensus Vit ERE whereas ER alpha showed greater activation at the divergent LH ERE. This differential activation was observed for a number of ligands including estradiol, estrone, bisphenol A, octylphenol and diethystilbestrol. These findings show that the nature of the ERE, as well as the ratio of ER subtypes in a particular cell/tissue, will influence whether particular estrogen responsive genes are activated in the presence of natural or xenobiotic estrogens.

Animals↗
PubMed2005

The cAMP response element binding protein modulates expression of the transient outward current: implications for cardiac memory.

OBJECTIVE: Long-term cardiac memory (LTCM), expressed as a specific pattern of T-wave change on ECG, is associated with 1) reduced transient outward potassium current (I(to)), 2) reduced mRNA for the pore-forming protein of I(to), Kv4.3, 3) reduced cAMP response element binding protein (CREB), and 4) diminished binding to its docking site on the DNA, the cAMP response element (CRE). We hypothesized a causal link between the decrease of the transcription factor CREB and down-regulation of I(to) and one of its channel subunits, KChIP2, in LTCM. METHODS: After three weeks of left ventricular pacing to induce LTCM (8 paced, 7 sham control dogs), epicardial KChIP2 mRNA and protein levels were assessed by real-time PCR and Western blotting. Mimicking the CREB down-regulation in LTCM, CREB was knocked down in situ in other dogs using adenoviral anti-sense. Effects on the action potential notch, reflecting I(to), were investigated in situ using monophasic action potential (MAP) recordings and at the cellular level by the whole-cell patch clamp technique. CREB binding in the KChIP2 promoter region was ascertained by electrophoretic mobility-shift assays. RESULTS: In LTCM, epicardial KChIP2 mRNA and protein were reduced by 62% and 76%, respectively, compared to shams (p < 0.05). CREB binding by the canine KChIP2 promoter region was demonstrated. CREB knockdown led to disappearance of the phase1 notch in MAP and ablation of I(to). CONCLUSIONS: These results strengthen the hypothesis that down-regulation of CREB-mediated transcription underlies the attenuation of epicardial I(to) in LTCM. They also emphasize that ventricular pacing exerts effects at a subcellular level contributing to memory and conceivably to other forms of cardiac remodeling.

Action Potentials↗
PubMed2001

Identification of a glucocorticoid-responsive element in the promoter region of the mouse tyrosine hydroxylase gene.

It has been known for nearly 30 years that glucocorticoid receptor stimulation induces increased tyrosine hydroxylase (TH) gene expression. However, the mechanism mediating this effect has remained elusive. Sequences with homology to known glucocorticoid-responsive elements (GRE) have been identified in the 5' flanking region of the TH gene of several vertebrate species, but none has been shown to be functional. To identify the GRE element(s) in the TH promoter, we generated chimeric constructs in which different lengths of the 5' flanking sequences of the mouse TH gene (3.6, 1.1 and 0.8 kb) were ligated to a luciferase reporter gene. Dexamethasone treatment increased luciferase expression only in cells transiently transfected with the construct containing 3.6 kb of the TH 5' flanking DNA. Co-administration of mifepristone (RU486), a glucocorticoid receptor antagonist, blocked this effect. We identified a TH-GRE sequence (5'-GGCACAGTGTGGTCT) in the mouse 5' flanking DNA between -2435 and -2421 from the transcription start. Responsiveness to dexamethasone was lost following deletion of this sequence. To determine the ability of this element to function in a heterologous promoter, we prepared a chimeric construct in which the TH-GRE sequence was cloned just upstream of a minimal thymidine kinase (TK) promoter. Promoter activity was increased 2-fold in dexamethasone-treated PC12 cells transfected with the TH-GRE-TK construct. These results provide strong evidence that the 15 base-pair sequence in the 5' flanking DNA of the mouse TH gene functions as a glucocorticoid response element. This is the first report identifying a functional glucocorticoid response element in the promoter region of the TH gene of any species.

Animals↗
PubMed1989

Computer analysis of 1,25-dihydroxyvitamin D3-receptor regulated promoters: identification of a candidate D3-response element.

The receptor for the steroid hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] belongs to a superfamily of steroid and triidothyronine (T3) receptors. As yet no 1,25(OH)2D3 response element (DRE) has been identified. Since the T3 and 1,25(OH)2D3 receptors are structurally homologous, we have used the nucleotide sequence of the T3 response element to carry out a computer search of the promoter region of several 1,25(OH)2D3 regulated genes. We report here one candidate DRE from the chick calbindin-D28K gene (AGCCCAATGGCTGAACA) and two candidate DRE's from the rat osteocalcin gene (TCCCCACTGGATGAGCG and CCTGCACTGGGTGAATGA).

Animals↗
PubMed1996

Insertion of metal-responsive elements increases the inducibility of the mouse mammary tumor virus promoter.

The promoter of the mouse mammary tumor virus (MMTV) is commonly used in inducible mammalian expression vectors. We have modified this promoter by inserting metal-responsive elements (MRE) at different sites. Surprisingly, MMTV promoters containing MRE 5' with respect to the glucocorticoid responsive elements (GRE), were not induced by metal ions. However, in the simultaneous presence of dexamethasone and metal ions, the modified promoters displayed a significantly increased transcriptional strength [up to sevenfold more than wild-type (wt) MMTV] in transiently transfected cells and permanent cell lines. This increment in the inducible expression was achieved without a concomitant increase in the basal level of expression. These modified MMTV promoters will offer the opportunity to develop tightly regulated inducible mammalian expression systems that are significantly more potent than the ones based on the wt MMTV promoter.

Animals↗
PubMed1999

The tissue-specific transcription factor Pit-1/GHF-1 binds to the c-fos serum response element and activates c-fos transcription.

Pit-1, a POU domain-containing transcription factor, is involved in two functions in the pituitary: PRL and GH tissue-specific expression and somatolactotroph cells expansion. To analyze the molecular basis of the latter function, we tested whether Pit-1 can directly transactivate expression of an early marker of cell cycle initiation, the c-fos gene. We show that Pit-1 overexpression in PC12 cells, which do not express Pit-1, increases c-fos expression. Moreover, cAMP-induced c-fos promoter activity is decreased in the somatolactotroph cell line GH3 when Pit-1 expression is reduced by hybrid arrest with an antisense sequence complementary to Pit-1 cDNA. In contrast to hormonal genes regulation, where it has been shown that any Pit-1 phosphorylation site is involved, we show that the Pit-1 phosphorylation sites are required to allow increase of c-fos promoter activity by Pit-1. We further show, by gel shift analyses, that Pit-1 is able to specifically bind the serum response element sequence present within the c-fos promoter but with a lesser affinity than the Pit-1 response element. Taken together, these results demonstrate that the tissue-specific transcription factor Pit-1 is able to enhance expression of genes involved in cell cycle initiation, suggesting that this mechanism allows Pit-1 to increase somato-lactotroph cell proliferation.

Animals↗
PubMed1997

Distal apolipoprotein C-III regulatory elements F to J act as a general modular enhancer for proximal promoters that contain hormone response elements. Synergism between hepatic nuclear factor-4 molecules bound to the proximal promoter and distal enhancer sites.

Transient transfection assays have shown that the distal apoC-III promoter segments that contain the regulatory elements F to J enhance the strength of the tandemly linked proximal apoA-I promoter 5- to 13-fold in hepatic (HepG2) cells. Activation in intestinal (CaCo-2) cells to levels comparable to those obtained in HepG2 cells requires a larger apoA-I promoter sequence that extends to nucleotide -1500 as well as the presence of hepatic nuclear factor-4 (HNF-4). The distal apoC-III regulatory elements can also enhance 4- to 8-fold the strength of the heterologous apoB promoter in HepG2 and CaCo-2 cells. Finally, these elements in the presence of HNF-4 enhance 14.5- to 18.5-fold the strength of the minimal adenovirus major late promoter linked to two copies of the hormone response element (HRE) AID of apoA-I in both HepG2 and CaCo-2 cells. In vitro mutagenesis of the promoter/enhancer cluster established that the enhancer activity is lost by a mutation in the HRE present in the 3' end of the regulatory element I (-736 to -714) and is reduced significantly by point mutations or deletions in one or more of the regulatory elements F to J of the apoC-III enhancer. The enhancer activity also requires the HREs of the proximal apoA-I promoter. The apoC-III enhancer can also restore the activity of the proximal apoA-I and apoB promoters that have been inactivated by mutations in CCAAT/enhancers binding protein binding sites, indicating that C/EBP may not participate in the synergistic activation of the promoter/enhancer cluster. The findings suggest that the regulatory elements F to J of the apoC-III promoter act as a general modular enhancer that can potentiate the strength of proximal promoters that contain HREs. Such potentiation in the HepG2 cells can be accounted for by synergistic interactions between HNF-4 or other nuclear hormone receptors bound to the proximal and distal HREs and SP1 or other factors bound to the apoC-III enhancer. Additional factors may be required for optimal activity in CaCo-2 cells as well as for the function of this region as an intestinal enhancer.

Apolipoproteins C↗
PubMed1996

Cooperative role of interferon regulatory factor 1 and p91 (STAT1) response elements in interferon-gamma-inducible expression of human indoleamine 2,3-dioxygenase gene.

Interferon (IFN)-gamma induces the expression of the indoleamine 2, 3-dioxygenase (INDO) gene in human cells, which plays a role in the inhibitory effect of IFN-gamma on intracellular pathogens and on cell proliferation. Earlier studies established that the IFN-gamma-inducible expression of the INDO gene was dependent on two upstream elements: (i) a 14-base pair sequence homologous to an interferon-stimulated response element (ISRE) sequence found in IFN-alpha-inducible genes and (ii) a 9-base pair palindromic sequence (palindromic element (PE) II) homologous to an interferon-gamma-activated site (GAS) element found in IFN-gamma-inducible genes. A second GAS element (PE I), between ISRE and PE II, was ineffective in supporting a response to IFN-gamma. Studies were carried out to determine the distinction between the two GAS elements and the relative role of the two elements (ISRE and PE II) required for a response to IFN-gamma. The PE I element was able to form a complex with IFN-gamma-activated p91 (STAT1) factor but with lower efficiency than the complex formed with PE II sequence. However, switching the positions of PE I and II sequences in reporter plasmid constructs (containing chloramphenicol acetyltransferase gene) showed that both PE I and PE II were able to support a response to IFN-gamma if located at the position of PE II but not at the position of PE I. Increasing the distance between the ISRE and PE II also affected the level of response, suggesting that the relative position of the two elements is important for optimal stimulus. To explore whether an interaction between the IFN-gamma-regulated factors (IRF-1 and p91) binding to the ISRE and PE II might be important, we tested whether the ISRE sequence could be replaced by another response element, NF-kappaB. The plasmid construct with NF-kappaB element in place of the ISRE was responsive to IFN-gamma, indicating that an interaction between the IRF-1 and p91 factors was not required. The results indicate that the response of INDO gene to IFN-gamma depends on a cooperative role of IFN-gamma-responsive factors binding to the ISRE and GAS elements.

Base Sequence↗
PubMed2001

Analysis of Usp DNA binding domain targeting reveals critical determinants of the ecdysone receptor complex interaction with the response element.

The steroid hormone, 20-hydroxyecdysone (20E), directs Drosophila metamorphosis via a heterodimeric receptor formed by two members of the nuclear hormone receptors superfamily, the product of the EcR (EcR) and of the ultraspiracle (Usp) genes. Our previous study [Niedziela-Majka, A., Kochman, M., Ozyhar, A. (2000) Eur. J. Biochem. 267, 507-519] on EcR and Usp DNA-binding domains (EcRDBD and UspDBD, respectively) suggested that UspDBD may act as a specific anchor that preferentially binds the 5' half-site of the pseudo-palindromic response element from the hsp27 gene promoter and thus locates the heterocomplex in the defined orientation. Here, we analyzed in detail the determinants of the UspDBD interaction with the hsp27 element. The roles of individual amino acids in the putative DNA recognition alpha helix and the roles of the base pairs of the UspDBD target sequence have been probed by site-directed mutagenesis. The results show how the hsp27 element specifies UspDBD binding and thus the polar assembly of the UspDBD/EcRDBD heterocomplex. It is suggested how possible nucleotide deviations within the 5' half-site of the element may be used for the fine-tuning of the 20E-response element specificity and consequently the physiological response.

Amino Acid Sequence↗
PubMed1996

Identification and characterization of basal and cyclic AMP response elements in the promoter of the rat hexokinase II gene.

Hexokinases catalyze the phosphorylation of glucose and initiate cellular glucose metabolism. Hexokinase II (HKII) is the principal hexokinase isoform in skeletal muscle, heart, and adipose tissue. Isoproterenol and exogenous cyclic AMP (cAMP) increase HKII gene transcription in L6 myotubes. Various segments of the HKII promoter that direct the expression of the chloramphenicol acetyltransferase reporter gene were transfected into L6 myotubes to identify basal and cAMP response elements. The 5'-flanking region that extends 90 base pairs upstream of the transcription start site includes a CCAAT box and a cAMP response element (CRE); both contribute to basal promoter activity and each provides an independent, maximal response to cAMP. An inverted CCAAT motif, or Y box, located just upstream of the CCAAT box, contributes to basal promoter activity but is not involved in the cAMP response. Homo- and heterodimers composed of the CRE-binding protein and activating transcription factor-1 bind specifically to the CRE. The Y box and the CCAAT box specifically bind the factor NF-Y (also known as CBF).

Animals↗
PubMed1994

Modulation by chronic morphine administration of single-stranded cAMP response element (ssCRE) binding proteins in the mouse cerebellum.

The development of opiate tolerance and dependence are thought to be associated with gene expression. Our previous studies have shown that the binding activity of nuclear factors to a single-stranded oligo-DNA containing cAMP response element (ssCRE) is altered by long term treatment with morphine in cultured neuronal cells. In the present experiments, the effects of acute and chronic treatments with morphine on the binding of nuclear proteins to single- and double-stranded oligo-DNAs of the cAMP response element were studied in the mouse brains by using gel shift assay. The activity of single-stranded CRE binding proteins (ssCRE-BP) was decreased by chronic morphine treatment to about 40% of control in the cerebellum. The effect of chronic morphine treatment on the binding activity persisted for at least 2 weeks after morphine withdrawal. The activity of double-stranded CRE binding proteins was also detected in the cerebellum, but it was insensitive to the morphine treatment. The activity of ssCRE-BP was also decreased by acute morphine treatment in 5 h, but it returned to control level in 24 h. These data suggest that the change of ssCRE-BP can be involved in the development of tolerance and dependence.

Animals↗
PubMed1991

Lovastatin selectively inhibits ras activation of the 12-O-tetradecanoylphorbol-13-acetate response element in mammalian cells.

To evaluate ras-mediated signal transduction, an alkaline phosphatase gene (SEAP) was placed under the control of the ras-inducible phorbol ester response element (TRE) in murine fibroblasts (TRE-SEAP cells). The Kirsten ras gene was placed under the control of the glucocorticoid-inducible mouse mammary tumor virus promoter and introduced into the TRE-SEAP cells. Dexamethasone increased ras expression in the TRE-SEAP cells carrying the Kirsten ras gene and stimulated SEAP activity 25-fold. Lavostatin blocked dexamethasone induction of SEAP activity (50% inhibitory concentration, 0.5 microM) but did not affect phorbol ester-induced SEAP activity in the same cells. Lovastatin also did not block forskolin induction of SEAP activity in cells expressing SEAP under the control of the cyclic AMP response element.

Alkaline Phosphatase↗
PubMed1998

Activity-regulated phosphorylation of cAMP response element binding protein in the developing striatum: implications for patterning the neurochemical phenotypes of striatal compartments.

A distinct feature of the striatum is that much of the expression of neurochemicals in this forebrain structure follows a compartmental (striosome/matrix) ordering. How this pattern of neurochemical compartmentation is developed and regulated is still unknown. In the present paper we propose that a key feature of this early striatal plasticity is differential control of the activation kinetics of the cAMP response element binding protein (CREB), which in turn influences striatal expression of genes containing cAMP response elements in their promoter sequences. Specifically, we propose that activity-dependent regulation of the kinetics of CREB phosphorylation, brought about early expressed protein phosphatases and protein phosphatase inhibitors in the developing striatal compartments, helps to set up and to maintain patterning of the neurochemical prototypes characteristic of striatal compartments.

Aging↗
PubMed2004

Regulation of antidepressant activity by cAMP response element binding proteins.

Depression is a clinically and biologically heterogeneous disease that is one of the most prevalent and costly psychiatric disorders. It is the leading cause of disability regarding job performance and burden on family members in the United States and worldwide. Although the therapeutic efficacy of antidepressant drugs has been recognized for years, the exact molecular mechanisms of action remain elusive, making the systematic approach to the development of new drugs difficult. The acute increases in levels of monoamines brought about by various classes of antidepressants cannot account for the requirement of repeated, chronic administration for up to 2-6 wk before treatment benefits become evident. Furthermore, despite their efficacy, current antidepressant drugs improve symptoms in only 60% of patients treated. The development of new and better therapies depends on a thorough understanding of the neurobiology of depression and the molecular mechanisms underlying antidepressant drug action. Early studies focusing on alterations in the levels of receptors and second messengers helped define the important signaling pathways initiated by these drugs, whereas recent molecular studies suggested that long-term adaptations in cellular signaling mechanisms may be required for the onset and/or maintenance of antidepressant effects. Attention has now focused on downstream targets of Ca++ and cyclic adenosine monophosphate (cAMP) in the cell, such as the activation of transcription factors. This article discusses the transcription factor cAMP response element binding protein and a related protein, cyclic AMP response element modulator, and their roles as molecular mediators of antidepressant action.

Animals↗
PubMed2004

Prostaglandin E2 induces MUC8 gene expression via a mechanism involving ERK MAPK/RSK1/cAMP response element binding protein activation in human airway epithelial cells.

MUC8 gene expression is overexpressed in nasal polyp epithelium and is also increased by treatment with inflammatory mediators in nasal epithelial cells. These data suggest that MUC8 may be one of important mucin genes expressed in human airway. However, the mechanisms of various inflammatory mediator-induced MUC8 gene expression in normal nasal epithelial cells remain unclear. We examined the mechanism by which prostaglandin E(2) (PGE2), an arachidonic acid metabolite, increases MUC8 gene expression levels. Here, we show that ERK mitogen-activated protein kinase is essential for PGE2-induced MUC8 gene expression in normal human nasal epithelial cells and that p90 ribosomal S 6 protein kinase 1 (RSK1) mediates the PGE2-induced phosphorylation of cAMP-response element binding protein. Our results also indicate that cAMP-response element at the -803 region of the MUC8 promoter is an important site of PGE2-induced MUC8 gene expression. In conclusion, this study gives insights into the molecular mechanism of PGE2-induced MUC8 gene expression in human airway epithelial cells.

Cell Line, Tumor↗
PubMed1995

YY1 facilitates the association of serum response factor with the c-fos serum response element.

YY1 is a multifunctional transcription factor that acts as an activator or repressor in different contexts. YY1 binds to multiple sites in the mouse c-fos promoter, inducing at each site a sharp DNA bend. Binding of YY1 to a site situated between the cyclic AMP response element (CRE) and the TATA box bends the DNA in a way that interferes with the interaction of proteins bound at the CRE and TATA elements, resulting in repression of transcription. Here, we show that binding of YY1 to a different site in the c-fos promoter has a different result. Binding of YY1 to the c-fos serum response element (SRE) enhances the binding of serum response factor (SRF). This enhancement requires the binding of YY1 to SRE DNA. YY1 and SRF can cooccupy the SRE at least transiently. In the region of overlapping contact, YY1 contacts DNA in the major groove, while SRF contacts DNA in the minor groove. YY1 also enhances the association of SRF with the SRE in transfected insect cells. Thus, although YY1 induces similar structural changes in DNA at different binding sites, it can have distinct local effects on protein-DNA and protein-protein interactions. These data support a general role for YY1 in the building of highly organized promoter complexes.

Animals↗
PubMed1992

Multiple DNA elements responsible for transcriptional regulation of the ornithine decarboxylase gene by protein kinase A.

Transcription of the ornithine decarboxylase (ODC) gene is rapidly elevated by activation of protein kinase A (PKA). The additive influence of three cis-acting elements is responsible for this regulation in an adrenal carcinoma cell line. Two sites, CRE2 at -48 base pairs (bp) relative to the start of transcription and CRE3 at +95 bp, are identical to the core motif of the cAMP-responsive element (CRE) of the somatostatin gene and are conserved in the mouse, rat, and human ODC genes. Mutation of CRE2 resulted in a substantial decrease in basal promoter activity, as well as a 5-fold decrease in inducibility of the ODC promoter by PKA. CRE3 did not contribute to the basal activity of the ODC promoter, but mutation of this site resulted in a 2-fold decrease in inducibility by PKA. Deletion of a 45-bp sequence (GC-box) located 5' of CRE2, also resulted in a 2-fold decrease in inducibility of the ODC promoter. DNase I protection revealed the presence of protein binding at CRE2, the TATA box, and the GC-box of the ODC promoter. Mutation of CRE2 resulted in loss of protection of this sequence, as well as the 3' extension of the footprint over the TATA box, without affecting interactions at the GC box. Antibodies to the well characterized CRE-binding protein CREB recognized proteins binding to CRE2, suggesting that binding of CREB, or an antigenically related protein, is important for the activity of CRE2. Additionally, recombinant CREB bound to a DNA probe containing the CRE2 sequence.

Adrenal Gland Neoplasms↗