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 811 records · Page 45Linked to original sources
PubMed1995

The response of the tyrosine hydroxylase gene to cyclic AMP is mediated by two cyclic AMP-response elements.

Tyrosine hydroxylase (TH) gene transcription rate is stimulated by cyclic AMP in cultured rat pheochromocytoma cells. This effect is at least partially due to the interaction of transcription factors with the canonical cyclic AMP-response element (CRE) at position -45 to -38 within the TH gene promoter. In this study we test whether a region of the TH gene promoter, which is adjacent to and upstream of the canonical TH CRE, also participates in the response of the promoter to cyclic AMP. Using electrophoretic mobility shift assays, we demonstrate that nuclear proteins from rat pheochromocytoma cell lines bind to the region of the TH gene from -102 to -73. A comparison of promoter sequences indicates that sequences within this region of the TH gene are highly homologous to proenkephalin promoter sequences (between -110 and -80) designated ENKCRE-1 and ENKCRE-2. We designated the TH gene sequence homologous to ENKCRE-1 as TH E1 and the sequence homologous to ENKCRE-2 as TH E2. Competition displacement binding assays suggest that protein binding to the -102/-73 region of the TH gene is critically dependent on the TH E1 sequence. Transient transfection assays using minimal promoter constructs demonstrate that this region acts as a cyclic AMP-responsive element. Mutagenesis of the TH E1 sequence within the normal context of the TH gene proximal promoter leads to a 50% decrease in the cyclic AMP inducibility of the promoter. These results support the hypothesis that the full response of the TH gene to cyclic AMP requires both the canonical TH CRE and this newly discovered element, which we term TH CRE2.

Adrenal Gland Neoplasms↗
PubMed1990

The PRE and PQ box are functionally distinct yeast pheromone response elements.

Saccharomyces cerevisiae mating pheromones function by binding to cell surface receptors and activating signal transduction processes which regulate gene expression. In this report, we have analyzed the minimum sequence requirements for conferring both a and alpha mating pheromone inducibilities onto a heterologous promoter. Here we show that the repetitive pheromone response element (PRE) which binds to STE12 protein is sufficient to confer pheromone responsiveness only when present in multiple copies. Moreover, by itself, it is preferentially responsive to alpha factor in a cells. In contrast, a single copy of the PQ box of the STE3 upstream activation sequence (UAS) is sufficient to confer a-factor responsiveness in alpha cells. The PQ box binds both MCM1 and MAT alpha 1 in a cooperative manner, and neither the P nor Q site alone is sufficient to confer a-factor responsiveness. In a cells, however, even multiple copies of the PQ box fail to confer alpha-factor responsiveness. Therefore, the PRE and the PQ box are functionally distinct pheromone-responsive elements with opposite cell type specificities. Moreover, these results indicate that the MCM1 protein functions in a signal transduction pathway in a manner analogous to that of its mammalian homolog, the serum response factor, which regulates the expression of the c-fos proto-oncogene in mammals.

Base Sequence↗
PubMed2002

The affinity and activity of the multiple hormone response element in the proximal promoter of the human oxytocin gene.

In vivo there appears to be a marked association between oestrogen levels and the expression of the oxytocin (OT) gene in most tissues. Transfection and DNA-protein binding experiments using high levels of either oestrogen receptor (ER)alpha or ERbeta imply a direct interaction of these transcription factors with the multiple hormone response element (HRE) at approximately -160 from the transcription start site of the OT gene in most species. In an extensive set of experiments, we show, using both transfection and protein-DNA binding, that low to moderate amounts of either oestrogen receptor, while being able to interact directly with a classic oestrogen response element (ERE) fail to interact with the human OT -160 HRE. Instead, this element, similar to its bovine counterpart, has a high affinity for the orphan receptors steroidogenic factor 1 and chicken ovalbumin upstream promoter transcription factor. Second, the human and bovine OT promoter can be made artificially responsive towards oestrogen in a cotransfection system over-expressing ERalpha or ERbeta, but not in cells expressing natural levels of these steroid receptors. Interestingly, nuclear extracts from both ERalpha-positive MCF7 cells and ERalpha-negative MDA-MB231 cells both contain a transcription factor which binds specifically to both the hOT-HRE element and to a classic ERE, and which has orphan receptor-like binding properties rather than those of an oestrogen receptor. Together, these and other results suggest that oestrogen action in vivo on the OT gene in all species is more likely to involve a DNA-independent mechanism than classic direct interactions with dimeric oestrogen receptors.

Animals↗
PubMed1992

Purification and characterization of cytosolic aconitase from beef liver and its relationship to the iron-responsive element binding protein.

In recent reports attention has been drawn to the extensive amino acid homology between pig heart, yeast, and Escherichia coli aconitases (EC 4.2.1.3) and the iron-responsive element binding protein (IRE-BP) of mammalian cells [Rouault, T. A., Stout, C. D., Kaptain, S., Harford, J. B. & Klausner, R. D. (1991) Cell 64, 881-883.; Hentze, M. W. & Argos, P. (1991) Nucleic Acids Res. 19, 1739-1740.; Prodromou, C., Artymiuk, P. J. & Guest, J. R. (1992) Eur. J. Biochem. 204, 599-609]. Iron-responsive elements (IREs) are stem-loop structures located in the untranslated regions of mRNAs. IRE-BP is required in the posttranscriptional regulation of ferritin mRNA translation and stabilization of transferrin receptor mRNA. In spite of substantial homology between the amino acid sequences of mammalian mitochondrial aconitase and IRE-BP, the mitochondrial protein does not bind IREs. However, there is a second aconitase, found only in the cytosol of mammalian tissues, that might serve as an IRE-BP. To test this possibility, we have prepared sufficient quantities of the heretofore poorly characterized beef liver cytosolic aconitase. This enzyme is isolated largely in its active [4Fe-4S] form and has a turnover number similar to that of mitochondrial aconitase. The EPR spectra of the two enzymes are markedly different. The amino acid composition, molecular weight, isoelectric point, and the sequences of six random peptides clearly show that these physicochemical and structural characteristics are identical to those of IRE-BP, and that c-aconitase is distinctly different from m-aconitase. In addition, both cytosolic aconitase and IRE-BP can have aconitase activity or function as IRE-BPs, as shown in the following paper and elsewhere [Zheng, L. Kennedy, M. C., Blondin, G. A., Beinert, H. & Zalkin, H. (1992) Arch. Biochem. Biophys., in press]. This leads us to the conclusion that cytosolic aconitase is IRE-BP.

Aconitate Hydratase↗
PubMed2005

Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: direct cross-talk between phase I and II drug-metabolizing enzymes.

The aryl hydrocarbon receptor (AHR) and NF-E2 p45-related factor (NRF2) are two distinct transcription factors involved in the regulation of drug-metabolizing enzymes. Increasing evidence from several studies implies that AHR and NRF2 have direct links, but the molecular mechanism remains unknown. In this work we demonstrate for the first time that Nrf2 gene transcription is directly modulated by AHR activation. DNA sequence analyses of the mouse Nrf2 promoter revealed one xenobiotic response element (XRE)-like element (XREL1) located at -712 and two additional XRE-like elements located at +755 (XREL2) and +850 (XREL3). Functional analysis using luciferase assay showed that XREL1, XREL2, and XREL3 are all inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment, with XREL2 being the most potent. The functionality of these XRE-like elements was further confirmed by mutagenesis and gel shift experiments. Finally, we used chromatin immunoprecipitation assay to show a direct binding of AHR to the Nrf2 promoter. Cells with silenced AHR expression using siRNA also lost NRF2 mRNA induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin. These new data position NRF2-antioxidant response element downstream in the AHR-XRE pathway. Moreover, direct regulation of NRF2 by AHR contributes to couple phase I and II enzymes into an integrated system facilitating more effective xenobiotic and carcinogen detoxification.

Animals↗
PubMed1993

Estrogen-responsive elements contain non-B DNA.

The estrogen receptor, a hormone-regulated transcription factor, regulates gene expression by interacting with a specific nucleotide sequence called the estrogen-responsive element (ERE). In this report we demonstrate by potassium permanganate, osmium tetroxide and diethylpyrocarbonate reactivity and S1 nuclease sensitivity that the nucleotides either within or in the immediate region of imperfect and perfect EREs are in a non-B DNA conformation. The presence of nucleotides in a non-B DNA conformation in the ERE is an intrinsic property of the DNA and is independent of whether the ERE is in linear or supercoiled DNA. S1 nuclease sensitivity was peculiar to the ERE as it was not detected in the thyroid hormone-responsive element. Our results suggest that the nucleotides comprising the ERE are structurally labile. We propose that this intrinsic lability of the ERE could be constrained in vivo such that a unique DNA tertiary structure is formed which may facilitate recognition of the ERE by the estrogen receptor.

Animals↗
PubMed2003

Multiple response elements and differential p53 binding control Perp expression during apoptosis.

The p53 tumor suppressor gene responds to cellular stress by activating either cell cycle arrest or apoptosis. A growing number of target genes involved in each of these pathways have been identified. However, the mechanism by which the apoptosis versus arrest decision is made remains to be elucidated. Perp is a proapoptotic target gene of p53 expressed to high levels in apoptotic cells compared with those undergoing cell cycle arrest. This pattern of expression is unusual among p53 target genes, many of which are induced to similar levels during arrest and apoptosis. Here, we describe the regulation of the Perp gene by p53 through at least three response elements in the Perp promoter and first intron. These sites are occupied in vivo in E1A-expressing mouse embryo fibroblasts undergoing apoptosis but not cell cycle arrest, in contrast to the p21 5' response element, which is occupied during both. The apoptosis-deficient p53 point mutant, p53V143A, displays a selective deficit in binding to the Perp elements, demonstrating that p53 can distinguish between Perp and p21 at the level of DNA binding. These results provide mechanistic insight into the selective expression of Perp during apoptosis and may provide a useful model for studying the p53-dependent cell cycle arrest versus apoptosis decision.

Animals↗
PubMed1999

Adeno-associated virus Rep78 binds to E2-responsive element 1 of bovine papillomavirus type 1.

Adeno-associated virus type-2 (AAV-2) is a helper-dependent parvovirus that has been implicated in the inhibition of replication and oncogenic transformation of bovine papillomavirus type-1 (BPV-1) and other transforming DNA viruses. Previous studies have suggested that the Rep78 protein of AAV-2 is a key player mediating this effect. In this report we have analyzed the effect of AAV-2 Rep78 protein on the regulation of gene expression of a reporter gene under the control of the long control region (LCR) of BPV-1. Our results show that Rep78 is capable of down-regulating the promoter activity of the LCR in vivo in tissue culture cells. Inhibition of LCR activity in vivo suggested the need for Rep78 to bind to a region of the LCR promoter spanning the E2-responsive elements of BPV-1. This observation was further confirmed in vitro with gel shift assays showing specific binding of Rep78 to DNA oligonucleotides containing E2-responsive element 1 (E2RE1) sequences of BPV-1 LCR. Our results expand the understanding of the mechanism of trans-regulation mediated by Rep78 and involving this protein and DNA sequences with complex secondary structure.

Animals↗
PubMed1995

A consensus insulin response element is activated by an Ets-related transcription factor.

Insulin increases expression of somatostatin-chloramphenicol acetyltransferase (CAT) constructs 10-fold and thymidine kinase-CAT constructs 5-fold in GH4 cells. These responses are similar to our previously reported data on insulin-increased prolactin-CAT expression. They are also observed in HeLa cells and are thus not cell type specific. The evidence suggests that the insulin responsiveness of these genes is mediated by an Ets-related transcription factor. First, linker-scanning mutations and/or deletions of the prolactin, somatostatin, and thymidine kinase promoters suggest that their insulin responsiveness is mediated by the sequence CGGA. This sequence is identical with the response element of the Ets-related transcription factors. Second, CGGA-containing sequences placed at -88 in the delta MTV-CAT reporter plasmid conferred insulin responsiveness to the mammary tumor virus promoter. Third, expression of the DNA-binding domain of c-Ets-2, which acts by blocking effects mediated by Ets-related transcription factors, inhibits the response of these promoters to insulin. Finally, the Ets-related proteins Sap and Elk-1 bind to the prolactin, somatostatin, and thymidine kinase insulin-response elements. An Ets-like element was found in all insulin-sensitive promoters examined and may serve a similar function in those promoters.

Animals↗
PubMed2000

Purification, identification, and characterization of an osmotic response element binding protein.

Kidney cells, especially the epithelial cells lining the collecting tubules in the inner medulla, are constantly exposed to concentrated urine. They are protected from the osmotic effect of high levels of sodium ion and urea by accumulating compatible osmolytes such as sorbitol, betaine, and myo-inositol. These osmolytes are involved in maintaining cell volume and electrolyte contents because they do not perturb the protein structure and function over a wide range of concentrations. Sorbitol is produced via the reduction of glucose by aldose reductase (AR), while betaine and myo-inositol are transported into the cells through specific transporters. Under hyperosmotic stress, transcriptions of genes encoding these proteins are highly induced. The induction of transcription was found to be mediated through the osmotic response elements (OREs) located in the 5' flanking sequences of these genes. We had earlier identified the OREs in human AR gene. In this study we purified and identified the osmotic response element binding protein (OREBP). OREBP is a transcription factor of approximately 200 kDa in size, characterized by a Rel-like DNA binding domain and a glutamine-rich transactivation domain. Dominant negative OREBP significantly diminished hyperosmotic AR gene induction. Immunohistochemical analysis showed that this transcription factor is rapidly translocated into the nucleus upon hyperosmotic stress.

Aldehyde Reductase↗
PubMed1988

Phosphorylation of serum response factor, a factor that binds to the serum response element of the c-FOS enhancer.

Serum and growth factor regulation of c-FOS protooncogene transcription is mediated by the serum response element. A factor, serum response factor, binding to this element has already been identified. We demonstrate that serum response factor is phosphorylated in vivo on serine residues and that phosphatase treatment of this factor in vitro abolishes its DNA-binding activity. These results show phosphorylation of serum response factor to be required for its DNA-binding activity. The importance of serum response factor phosphorylation for the regulation of c-FOS expression is discussed.

Animals↗
PubMed2000

Secalonic acid D alters the nature of and inhibits the binding of the transcription factors to the phorbol 12-O-tetradecanoate-13 acetate-response element in the developing murine secondary palate.

Secalonic acid D (SAD), a mycotoxin produced by Penicillium oxalicum in corn, induces cleft palate (CP) in the offspring of exposed dams. Results of recent studies suggest that protein kinase C (PKC) inhibition by SAD may be relevant to its CP-induction. Downstream effects of PKC are determined by the nature of transcription factors (TF) that form the activator protein-1 (AP-1) and the binding of AP-1 (and other TF) to the phorbol 12-O-tetradecanoate-13 acetate-response element (TRE) to form AP-1-TRE complex, neither of which have been studied in the palate. The aims of the present study were to identify the components of the murine palatal AP-1-TRE complex during development and to uncover the effects of SAD on this complex. Western blots and gel mobility shift assays of control palatal nuclear extracts revealed that, although all relevant TF are present in the palate throughout development, only cyclic-AMP response element (CRE) binding protein (CREB) and CRE-modulator protein-1 (CREM-1) and activating transcription factor-1 bound to TRE on Gestation Day (GD) 12. The pattern shifted to c-Jun and c-Fos (known AP-1 components) on GD 13 and 14. In SAD-treated offspring, however, CREM-1 alone; c-Jun, c-Fos, and CREB; and c-Jun and c-Fos bound to TRE on GD 12, 13, and 14, respectively. Binding of TF to TRE was inhibited by SAD on both GD 12 and 13. These results suggest that a dynamic shift in the binding of TF to TRE from PKA- to PKC-responsive TF occurs during palate development and that teratogens such as SAD can alter both the nature and extent of TF binding to TRE.

Animals↗
PubMed2004

Thyroid hormone positively regulates the enterocyte differentiation marker intestinal alkaline phosphatase gene via an atypical response element.

Thyroid hormone (T3) is a critical regulator of intestinal epithelial development and homeostasis, but its mechanism of action within the gut is not well understood. We have examined the molecular mechanisms underlying the T3 activation of the enterocyte differentiation marker intestinal alkaline phosphatase (IAP) gene. RT-PCR and Western blotting showed that thyroid hormone receptors TRalpha1 and TRbeta1 were expressed in human colorectal adenocarcinoma Caco-2 cells. Northern blotting detected expression of two IAP transcripts, which were increased approximately 3-fold in response to T3. Transient transfection studies with luciferase reporter plasmids carrying various internal and 5' deletion mutations of the IAP promoter localized a putative thyroid hormone response element (TRE) to a region approximately 620 nucleotides upstream (-620) of the ATG start codon. EMSAs using TRalpha1-retinoid X receptor alpha (RXRalpha) on sequential 5' and 3' single nucleotide deletions defined the TRE between -632 and -612 (5'-TTGAACTCAgccTGAGGTTAC-3'). Compared with the consensus TRE, the IAP-TRE is novel in that it contains an everted repeat of two nonamers (not hexamers) separated by three nucleotides. Neither TRalpha1 nor RXRalpha binds to the IAP-TRE; however, TRbeta1 binds to this TRE with minimal affinity. In the presence of TR and RXRalpha, only the TR-RXRalpha heterodimer binds to the IAP-TRE. Mutagenesis of either nonamer abolishes the biological activity of IAP promoter. We have thus identified a novel response element that appears to mediate the T3-induced activation of the enterocyte differentiation marker, intestinal alkaline phosphatase.

Alkaline Phosphatase↗
PubMed2002

Insulin-stimulated fatty acid synthase gene expression does not require increased sterol response element binding protein 1 transcription in primary adipocytes.

Sterol response element binding protein 1c (SREBP-1c) is a transcription factor that has been implicated in the regulation of expression of key lipogenic genes in hepatocytes, including fatty acid synthase (FAS) and glucokinase. In hepatocytes, insulin stimulates a rapid increase in transcription of SREBP-1c and the appearance of the SREBP-1c protein in the nucleus. SREBP-1 has also been proposed to play an important role in the induction of expression of lipogenic enzymes in adipose tissue in vivo in response to nutritional status. In this paper we have investigated the regulation of the SREBP-1 and FAS genes in adipocytes and find that while an overexpressed constitutively active SREBP-1 mutant is capable of substantially stimulating the FAS promoter, insulin appears to stimulate FAS gene expression in primary adipocytes in the absence of any apparent effect on SREBP-1 transcription. Taken together, our data suggest that insulin does not stimulate FAS gene expression through increasing SREBP-1c transcription in adipose cells.

Adipocytes↗
PubMed1990

Binding of trans-dominant mutant Rev protein of human immunodeficiency virus type 1 to the cis-acting Rev-responsive element does not affect the fate of viral mRNA.

The binding of Rev protein of human immunodeficiency virus type 1 (HIV-1) to the cis-acting Rev-responsive element (RRE) was compared to the binding of a trans-dominant Rev mutant. RevBL, which inhibits Rev function. Rev and RevBL expressed in bacteria were purified and shown to bind in vitro to the RRE with similar affinities. The study of the RRE mutants indicated that Rev and RevBL bind to the same target within the RRE in vitro and in vivo. In vivo experiments demonstrated that RevBL did not increase the steady-state levels of HIV-1 mRNA or protein. These experiments suggested that additional cellular factors interacting with Rev but not with RevBL are necessary for function. The Rex protein of human T-cell leukemia virus type I (HTLV-I) is similar to Rev and acts through a sequence named Rex-responsive element (RXRE) located in the long terminal repeat of HTLV-I. We examined the function of RevBL on a hybrid mRNA molecule containing both the RRE and RXRE. While RevBL prevented Rev function, it did not affect Rex function on the mRNA containing either the RXRE or both the RRE and RXRE. Therefore, binding of RevBL to the RRE had neither positive nor negative effects on the mRNA, since this mRNA could be efficiently utilized in the presence of a functional Rex-RXRE interaction. The results obtained in vivo and in vitro strongly suggest that RevBL inhibits Rev function by binding to the same site as Rev and preventing Rev binding and function.

Gene Expression Regulation, Viral↗
PubMed2004

Identification of an androgen response element in intron 8 of the sterol regulatory element-binding protein cleavage-activating protein gene allowing direct regulation by the androgen receptor.

Sterol regulatory element-binding proteins (SREBPs) are transcription regulators that play a pivotal role in intracellular lipid homeostasis. They are synthesized as inactive precursor proteins in the endoplasmic reticulum, where they are retained by SREBP cleavage-activating protein (SCAP), a sterol sensing protein that in turn is linked to a retention protein complex. Low intracellular sterol concentrations weaken the interaction of SCAP with its retention proteins and allow translocation of the SREBP.SCAP complex to the Golgi compartment where SREBP is proteolytically cleaved and activated. Previous studies on the mechanisms by which androgens provoke a coordinated activation of lipogenic pathways in prostate cancer cells have suggested an alternative pathway of activation in which androgens increase the expression of SCAP and favor translocation of the SREBP.SCAP complex to the Golgi apparatus by disturbing the balance between SCAP and its retention proteins. Here we show that the SCAP gene contains an androgen-responsive region located in intron 8. This region interacts directly with the androgen receptor and confers androgen responsiveness to promoter-reporter constructs transfected in LNCaP cells. It contains a noncanonical androgen response element GGAAGAaaaTGTACC that interacts not only with the androgen receptor but also with the glucocorticoid receptor and that also confers glucocorticoid responsiveness. The identification of a steroid response element in intron 8 of the SCAP gene further supports the contention that SCAP is a direct target for steroid hormone action.

Amino Acid Motifs↗
PubMed2001

Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes.

It has been shown that UVB irradiation induces expression of COX-2 and up-regulation of COX-2 plays a functional role in UVB tumor promotion. In this study, we examined the cis-elements in the human COX-2 promoter that may be responsible for the UVB induction of COX-2. Analyses with the COX-2 promoter region revealed that the cyclic AMP responsive element near the TATA box was essential for both basal and UVB induced COX-2 expression. This was further supported by studies using a dominant negative mutant of CREB, which strongly inhibited the activity of COX-2 promoter. Electrophoretic mobility shift assays indicated that CREB and ATF-1 were the major proteins binding to the COX-2 CRE. CREB and ATF-1 were phosphorylated upon UVB treatment, and SB202190, a p38 MAPK inhibitor, decreased the phosphorylation of CREB/ATF-1 and suppressed COX-2 promoter activity. In contrast, treatment with forskolin, an activator of adenylyl cyclase, led to phosphorylation of CREB and ATF-1 and activation of COX-2 promoter. Finally, enhanced binding of phospho-CREB/ATF-1 to the COX-2 CRE was observed after UVB induction. Thus, one signaling pathway for UVB induction of human COX-2 involves activation of p38, subsequent phosphorylation of CREB/ATF-1, and activation of the COX-2 CRE through enhanced binding of phosphorylated CREB/ATF-1.

Activating Transcription Factor 1↗
PubMed1993

Modulation of host cell nuclear proteins that bind to HIV-1 trans-activation-responsive element RNA by phorbol ester.

The trans-activation-responsive (TAR) element located within the 5' untranslated region of HIV-1 mRNA is the cis-responsive element for Tat, the viral trans-activator protein. Several TAR RNA binding proteins (TRBPs) have been identified in the nuclear extract from HeLa cells as cellular factors required for a full Tat-mediated trans-activation. In this study, we have tried to identify TRBPs in human T cell line (MOLT-4) persistently infected with HIV-1. Nuclear extract from the infected MOLT-4 cells was analyzed by gel-retardation and uv cross-linking assays with radiolabeled TAR RNA probe. Two major complexes of TAR RNA with some cellular proteins were detected in the gel-retardation assay. As the components of these complexes, at least five TRBPs (p30, p37, p46, p50, and p56) showing specific binding to the TAR RNA were detected in the uv cross-linking assay. We also observed that the detectable levels of p37 and p50 in the infected MOLT-4 cells were greatly reduced after phorbol ester (TPA) treatment under the condition of which HIV-1 gene expression was increased by about fivefold. These results suggest that the modulation of TRBPs by some mitogenic stimuli such as TPA might have a role in the trans-activation of HIV-1 gene expression in vivo.

Binding Sites↗