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At least 397 records · Page 22Linked to original sources
PubMed1988

Transcriptional activation of lck by retrovirus promoter insertion between two lymphoid-specific promoters.

p56lck, a member of the src family of cytoplasmic tyrosine protein kinases, is expressed primarily in lymphoid cells. Previous RNase protection data demonstrated the existence of at least two lck mRNAs (type I and type II) with different 5' untranslated regions in most T cells. These have been found here to arise from two separate promoters. S1 nuclease analysis and primer extension were used to locate the site of initiation of type I lck mRNA. The nucleotide sequence of the region upstream of this start site contains no classical promoter motifs. A cDNA clone of type II lck mRNA was isolated. The promoter of this mRNA must be more than 10 kilobases upstream of the type I promoter region. In two murine thymoma cell lines, LSTRA and Thy19, lck is expressed at elevated levels as a result of Moloney murine leukemia virus retrovirus promoter insertion. p56lck is encoded in these cells by a hybrid virus-lck mRNA containing the 5' untranslated region of Moloney virus mRNA. The structures and the sites of integration of the proviruses upstream of lck in these cells were examined by molecular cloning and Southern analysis. A truncated and rearranged provirus, flanked by 554 nucleotides (nt) of duplicated cellular sequences, was found 962 nt upstream of the start site for type I lck mRNA in LSTRA cells. What appears to be a Moloney mink cytopathic focus-forming provirus was found between 584 to 794 nt upstream of the start site for type I lck mRNA in Thy19 cells. Thus in both tumor cell lines, viral DNA is present between the promoters for type I and type II lck mRNAs. Comparison of the sequences of the 5' ends of the lck and c-src genes suggests that divergence of these two genes involved exon shuffling and that a homolog of the neuronal c-src(+) exon is not present in lck.

Animals↗
PubMed1988

EIa-mediated stimulation of the adenovirus EIII promoter involves an enhancer element within the nearby EIIa promoter.

The transcriptional induction of adenovirus early genes by the viral immediate early gene EIa constitutes an attractive model system for the study of control mechanisms involved in eucaryotic promoter function. The EIa-mediated activation of the divergently transcribed EIIa early (EIIaE) and EIII promoters was investigated in experiments in which recombinant plasmids containing the entire EIIa-EIII control region were cotransfected with a plasmid expressing the EIa 13S mRNA. First, both promoters were activated by low levels of EIa, but the extent of EIII induction decreased with increasing EIa concentrations, whereas EIIaE stimulation remained unchanged. Second, transcriptional analysis of deletion mutants revealed that an element of the EIIaE promoter contributed to maximal EIa responsiveness of the nearby EIII promoter. This element, located between positions -82 and -71 with respect to the EIIaE major cap site, corresponded to the central portion of an EIa-dependent enhancer, originally mapped between about -110 and -50 (P. Jalinot and C. Kédinger, Nucleic Acids Res. 14:2651-2669, 1986). The implication of these observations in the coordinate expression from the EIIaE and EIII promoters during lytic infection is discussed.

Adenovirus Early Proteins↗
PubMed1990

Transcriptional activation of the adenine phosphoribosyltransferase promoter by an upstream butyrate-induced Moloney murine sarcoma virus enhancer-promoter element.

It has been documented that the activity of a specific promoter can be occluded by the presence of another promoter element upstream. We present evidence for a phenomenon contradictory to that predicted by the promoter occlusion theory. Transcription from the hamster aprt (adenine phosphoribosyltransferase) promoter was augmented instead of repressed in transfected mouse L cells when an upstream Moloney murine sarcoma virus enhancer-promoter element was induced with butyrate. Without an adjacent Moloney murine sarcoma virus element, butyrate could not activate the aprt promoter.

Adenine Phosphoribosyltransferase↗
PubMed1996

Activation of the human thymidine kinase (TK) promoter by simian virus 40 large T antigen requires both the T antigen pRb family-binding domain and TK promoter sequences resembling E2F-binding sites.

Infection of quiescent cells with the DNA tumor virus simian virus 40 induces expression of the cellular thymidine kinase (TK) gene a minimum of 10- to 20-fold, and this induction depends upon the viral protein large T antigen (T-Ag). To define both human TK promoter elements and T-Ag functional domains required for transcriptional induction, we have established a system in which stable Rat-1 transfectants harboring TK promoter-luciferase hybrid genes are infected with recombinant adenoviruses expressing either wild-type or mutant forms of T-Ag and luciferase expression is measured as an indicator of promoter activity. The results show that (i) a 135-bp TK promoter fragment is activated 10- to 15-fold by viral infection; (ii) this activation is the result of both T-Ag-dependent and -independent mechanisms; (iii) the T-Ag pRb family-binding domain, but not the p53-binding, helicase, or ATPase domain, is required for activation; and (iv) activation is severely diminished with a TK promoter fragment in which E2F-like-binding sites have been removed. These data demonstrate a requirement for both an E2F-related factor and a pRb family member in activation of the TK promoter by T-Ag. This contrasts with the promiscuous activation of many cellular and viral genes by T-Ag, which is independent of its ability to bind pRb.

Animals↗
PubMed1999

Spatial perturbations within an RNA promoter specifically recognized by a viral RNA-dependent RNA polymerase (RdRp) reveal that RdRp can adjust its promoter binding sites.

RNA synthesis during viral replication requires specific recognition of RNA promoters by the viral RNA-dependent RNA polymerase (RdRp). Four nucleotides (-17, -14, -13, and -11) within the brome mosaic virus (BMV) subgenomic core promoter are required for RNA synthesis by the BMV RdRp (R. W. Siegel et al., Proc. Natl. Acad. Sci. USA 94:11238-11243, 1997). The spatial requirements for these four nucleotides and the initiation (+1) cytidylate were examined in RNAs containing nucleotide insertions and deletions within the BMV subgenomic core promoter. Spatial perturbations between nucleotides -17 and -11 resulted in decreased RNA synthesis in vitro. However, synthesis was still dependent on the key nucleotides identified in the wild-type core promoter and the initiation cytidylate. In contrast, changes between nucleotides -11 and +1 had a less severe effect on RNA synthesis but resulted in RNA products initiated at alternative locations in addition to the +1 cytidylate. The results suggest a degree of flexibility in the recognition of the subgenomic promoter by the BMV RdRp and are compared with functional regions in other DNA and RNA promoters.

Promoter Regions, Genetic↗
PubMed2006

Binding of YY1 to the proximal region of the murine beta interferon promoter is essential to allow CBP recruitment and K8H4/K14H3 acetylation on the promoter region after virus infection.

Virus-induced activation of the beta interferon (IFN-beta) gene requires orderly recruitment of chromatin-remodeling complexes and time-regulated acetylation of histone residues K8H4 and K14H3 on the promoter region. We have previously shown that transcription factor Yin Yang 1 (YY1) binds the murine IFN-beta promoter at two sites (-122 and -90) regulating promoter transcriptional capacity with a dual activator/repressor role. In this work we demonstrate that both YY1 -122 and -90 sites are required for CBP recruitment and K8H4/K14H3 acetylation to take place on the IFN-beta promoter region after virus infection. A single point mutation introduced at either one of these two sites inhibiting YY1 binding completely disrupted CBP recruitment and K8H4/K14H3 acetylation independently of HMGI or IRF3 binding to the promoter. We have previously demonstrated that YY1 represses the transcriptional capacity of the IFN-beta promoter through its -90 site via histone deacetylation. Here we demonstrate that, in vivo, the binding of YY1 to the -90 site is constant all through virus infection whereas the binding of YY1 to the -122 site is activated after infection. We discuss here the capacity of YY1 to either repress (through histone deacetylase recruitment) or activate (through CBP recruitment) IFN-beta gene expression according to the occupancy of either only its -90 site or both its -122 and -90 sites.

Acetylation↗
PubMed1993

An opportunistic promoter sharing regulatory sequences with either a muscle-specific or a ubiquitous promoter in the human aldolase A gene.

The human aldolase A gene is transcribed from three different promoters, pN, pM, and pH, all of which are clustered within a small 1.6-kbp DNA domain. pM, which is highly specific to adult skeletal muscle, lies in between pN and pH, which are ubiquitous but particularly active in heart and skeletal muscle. A ubiquitous enhancer, located just upstream of pH start sites, is necessary for the activity of both pH and pN in transient transfection assays. Using transgenic mice, we studied the sequence controlling the muscle-specific promoter pM and the relations between the three promoters and the ubiquitous enhancer. A 4.3-kbp fragment containing the three promoters and the ubiquitous enhancer showed an expression pattern consistent with that known in humans. In addition, while pH was active in both fast and slow skeletal muscles, pM was active only in fast muscle. pM activity was unaltered by the deletion of a 1.8-kbp region containing the ubiquitous enhancer and the pH promoter, whereas pN remained active only in fast skeletal muscle. These findings suggest that in fast skeletal muscle, a tissue-specific enhancer was acting on both pN and pM, whereas in other tissues, the ubiquitous enhancer was necessary for pN activity. Finally, a 2.6-kbp region containing the ubiquitous enhancer and only the pH promoter was sufficient to bring about high-level expression of pH in cardiac and skeletal muscle. Thus, while pH and pM function independently of each other, pN, remarkably, shares regulatory elements with each of them, depending on the tissue. Importantly, expression of the transgenes was independent of the integration site, as originally described for transgenes containing the beta-globin locus control region.

Animals↗
PubMed1993

Enhancer-dependent transcription of the epsilon-globin promoter requires promoter-bound GATA-1 and enhancer-bound AP-1/NF-E2.

We analyzed epsilon-globin transcription in erythroid cells and in erythroid extracts to determine the requirements for enhancer-dependent expression of this gene. Mutations that abolished GATA-1 binding at a single position in the promoter prevented interaction with enhancers, whereas elimination of a second more distal promoter GATA-1 site had no effect. Deletion or mutation of the GATA-1 sites in either the human beta-globin locus control region DNase-hypersensitive site II enhancer or the chicken beta A/epsilon-globin enhancer did not diminish the ability of the enhancers to interact with the promoter. In contrast, mutation of the AP-1/NF-E2 sites in these enhancers resulted in elimination of enhancement. In vitro transcription of these constructs was promoter dependent and was not sensitive to abolition of GATA-1 binding in the promoter, consistent with the role of GATA-1 solely as a mediator of the enhancer effect. Thus, GATA-1 regulates the response of the epsilon-globin gene to enhancers through a specific site in the promoter and requires enhancer AP-1/NF-E2 binding to transduce the enhancer effect on transcription.

Base Sequence↗
PubMed2001

runt homology domain transcription factors (Runx, Cbfa, and AML) mediate repression of the bone sialoprotein promoter: evidence for promoter context-dependent activity of Cbfa proteins.

Expression of the bone sialoprotein (BSP) gene, a marker of bone formation, is largely restricted to cells in mineralized tissues. Recent studies have shown that the Cbfa1 (also known as Runx2, AML-3, and PEBP2alphaA) transcription factor supports commitment and differentiation of progenitor cells to hypertrophic chondrocytes and osteoblasts. This study addresses the functional involvement of Cbfa sites in expression of the Gallus BSP gene. Gel mobility shift analyses with nuclear extracts from ROS 17/2.8 osteoblastic cells revealed that multiple Cbfa consensus sequences are functional Cbfa DNA binding sites. Responsiveness of the 1.2-kb Gallus BSP promoter to Cbfa factors Cbfa1, Cbfa2, and Cbfa3 was assayed in osseous and nonosseous cells. Each of the Cbfa factors mediated repression of the wild-type BSP promoter, in contrast to their well known activation of various hematopoietic and skeletal phenotypic genes. Suppression of BSP by Cbfa factors was not observed in BSP promoters in which Cbfa sites were deleted or mutated. Expression of the endogenous BSP gene in Gallus osteoblasts was similarly downregulated by forced expression of Cbfa factors. Our data indicate that Cbfa repression of the BSP promoter does not involve the transducin-like enhancer (TLE) proteins. Neither coexpression of TLE1 or TLE2 nor the absence of the TLE interaction motif of Cbfa1 (amino acids 501 to 513) influenced repressor activity. However, removal of the C terminus of Cbfa1 (amino acids 362 to 513) relieved suppression of the BSP promoter. Our results, together with the evolutionary conservation of the seven Cbfa sites in the Gallus and human BSP promoters, suggest that suppressor activity by Cbfa is of significant physiologic consequence and may contribute to spatiotemporal expression of BSP during bone development.

Animals↗
PubMed1986

Cellular promoters incorporated into the adenovirus genome: effects of viral regulatory elements on transcription rates and cell specificity of albumin and beta-globin promoters.

In the accompanying paper (Friedman et al., Mol. Cell. Biol. 6:3791-3797, 1986), hepatoma-specific expression of the rat albumin promoter within the adenovirus genome was demonstrated. However, the rate of transcription was very low compared with that of the endogenous chromosomal albumin gene. Here we show that in hepatoma cells the adenovirus E1A enhancer, especially in the presence of E1A protein, greatly stimulates transcription from the albumin promoter but not the mouse beta-globin promoter. This enhancer-dependent stimulation did not occur in myeloma cells in which a virus containing a immunoglobulin promoter and enhancer did function. These experiments suggest a limited distribution in cultured differentiated cells of cell-specific transcription factors. However, either the regulation of such cell-specific factors breaks down in other cultured cells, or strictly cell-specific factors are not at play in controlling cell-specific transcription, because HeLa cells could transcribe the albumin promoter from the same start site about 10% as well as hepatomas could and 293 cells could transcribe both albumin and globin promoters.

Adenovirus Early Proteins↗
PubMed1988

SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat.

We developed a novel promoter system, designated SR alpha, which is composed of the simian virus 40 (SV40) early promoter and the R segment and part of the U5 sequence (R-U5') of the long terminal repeat of human T-cell leukemia virus type 1. The R-U5' sequence stimulated chloramphenicol acetyltransferase (CAT) gene expression only when placed immediately downstream of the SV40 early promoter in the sense orientation. The SR alpha expression system was 1 or 2 orders of magnitude more active than the SV40 early promoter in a wide variety of cell types, including fibroblasts and lymphoid cells, and was capable of promoting a high level of expression of various lymphokine cDNAs. These features of the SR alpha promoter were incorporated into the pcD-cDNA expression cloning vector originally developed by Okayama and Berg.

Animals↗
PubMed1994

Identification of a novel first exon in the human dystrophin gene and of a new promoter located more than 500 kb upstream of the nearest known promoter.

The dystrophin gene, which is mutated in patients with Duchenne and Becker muscular dystrophies, is the largest known human gene. Five alternative promoters have been characterized until now. Here we show that a novel dystrophin isoform with a different first exon can be produced through transcription initiation at a previously unidentified alternative promoter. The case study presented is that of a patient with Duchenne muscular dystrophy who had a deletion extending from the 5' end of the dystrophin gene to exon 2, including all promoters previously mapped in the 5' part of the gene. Transcripts from lymphoblastoid cells were found to contain sequences corresponding to exon 3, indicating the presence of new promoter upstream of this exon. The nucleotide sequence of amplified cDNA corresponding to the 5' end of the new transcript indicated that the 5' end of exon 3 was extended by 9 codons, only the last (most 3') of which codes for methionine. The genomic nucleotide sequence upstream from the new exon, as determined using inverse polymerase chain reaction, revealed the presence of sequences similar to a TATA box, an octamer motif and an MEF-2 element. The identified promoter/exon did not map to intron 2, as might have been expected, but to a position more than 500 kb upstream of the most 5' of the previously identified promoters, thereby adding 500 kb to the dystrophin gene. The sequence of part of the new promoter region is very similar to that of certain medium reiteration frequency repetitive sequences. These findings may help us understand the molecular evolution of the dystrophin gene.

Amino Acid Sequence↗
PubMedDate not supplied

Strong, long-term transgene expression in rat liver using chicken beta-actin promoter associated with cytomegalovirus immediate-early enhancer (CAG promoter).

For successful gene therapy in hepatic enzyme deficiencies, it is essential to use promoters that can maintain strong transcriptional activity for the long term in the liver. Using Gunn rats, a model animal for Crigler-Najjar syndrome type I, the long-term transcriptional function of the CAG promoter (a combination of chicken beta-actin promoter and cytomegalovirus immediate-early enhancer) was evaluated in the rat liver. We constructed a plasmid pCAGGHUGT, containing expression cassettes of human bilirubin UDP-glucuronosyltransferase (BUGT) and hygromycin phosphotransferase, under the control of the CAG promoter and murine phosphoglycerate kinase promoter, respectively. Conditionally immortalized Gunn rat hepatocytes (IGRH), which had been established using mutant SV40 large T antigen ((TS)T), were transfected with pCAG-GHUGT. A stably transfected clone IGRHUGT, expressing a high level of BUGT, was obtained after selection with hygromycin. At 33 degrees C, the cells doubled in number in approximately 72 h; however, at 37 degrees C, cell proliferation stopped, indicating that the characteristic of temperature-dependent proliferation was retained in this clone. Ten million cells were injected into the spleen of syngeneic Gunn rats five times at 10-day intervals. Serum bilirubin levels were reduced by 45-50% at 70 days after the first transplantation and remained so throughout the duration of the study (120 days). These results suggested that the CAG promoter was able to maintain strong transcriptional activity in rat liver for at least 120 days.

Actins↗
PubMed2004

Environmental health promotion: bridging traditional environmental health and health promotion.

This article highlights the juncture between environmental health and health promotion and underscores the need for health promotion involvement in environmental health practice. It begins with a synopsis of current issues in environmental public health and deficiencies in environmental public health practice that could be partly ameliorated by an increased focus on environmental health promotion. Environmental health promotion lies at the intersection between the two disciplines and can be defined as any planned process employing comprehensive health promotion approaches to assess, correct, control, and prevent those factors in the environment that can potentially harm the health and quality of life of present and future generations. An introduction is also provided to the six articles contained in this special issue focused on environmental health promotion, and a brief discussion of crosscutting themes and issues is presented.

Environmental Health↗
PubMed2003

A CYP7A promoter binding factor site and Alu repeat in the distal promoter region are implicated in regulation of human CETP gene expression.

The cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol transport in mediating the transfer of cholesteryl ester from HDL to atherogenic apolipoprotein B-containing lipoproteins (VLDL, IDL, and LDL). Variation in plasma CETP mass in both normolipidemic and dyslipidemic individuals may reflect differences in CETP gene expression. As the 5' flanking sequence up to 3.4 kb of the human CETP gene contributes to transcriptional activity and tissue-specific gene expression, we evaluated the role of the distal promoter region in the modulation of CETP gene expression. In transfection experiments in HepG2 cells, we presently demonstrate that an Alu repeat (-2,153/-2,414) acts as a repressive element, whereas a binding site for the orphan nuclear receptor CYP7A promoter binding factor (CPF), at position -1,042, facilitates activation of human CETP promoter activity. Cotransfection of liver receptor homolog, the mouse homologue of CPF in HEK293 cells that lack CPF, indicated that the -1,042 CPF site is sufficient to induce CPF-mediated activation of CETP promoter activity. Taken together, our results indicate that the distal-promoter region is a major component in the modulation of human CETP promoter activity, and that it may contribute to the liver-specific expression of the CETP gene.

Alu Elements↗
PubMed2004

Contrasting mammalian parathyroid hormone (PTH) promoters: nuclear factor-Y binds to a deoxyribonucleic acid element unique to the human PTH promoter and acts as a transcriptional enhancer.

The identification of a highly conserved specificity protein 1 (Sp1) DNA element in mammalian PTH promoters was recently reported. However, the presence of a novel DNA-binding complex was subsequently observed exclusively with the human PTH (hPTH) Sp1 element in mobility shift studies. Point mutations in the hPTH Sp1 element revealed the factor recognized a CAAT-like sequence resulting from a single nucleotide difference unique to the human sequence relative to other mammalian promoters. A consensus nuclear factor Y (NF-Y) element was able to specifically compete for formation of the novel complex, whereas antiserum directed against the B-subunit of NF-Y supershifted the complex without disturbing binding by the Sp3/Sp1 proteins. Moreover, immunocytochemistry confirmed the nuclear localization of NF-Y in parathyroid gland cells. Transient expression of a dominant negative form of NF-Y impaired basal hPTH promoter activity in opossum kidney cells. Studies in Drosophila SL2 cells revealed that an intact NF-Y complex was required to strongly activate transcription from the hPTH promoter, and mutational analysis confirmed the identity of the NF-Y and Sp1 DNA elements. Finally, coexpression studies in SL2 cells indicated that NF-Y and Sp1 competed for binding to their adjoining sites in the hPTH promoter. In summary, an NF-Y enhancer DNA element has been identified that is uniquely positioned in the hPTH promoter and partially overlaps with the species-conserved Sp1 element. Binding appears to be mutually exclusive by the two transcription factors to this site and suggests that separate signaling pathways may be using this DNA locus to enhance transcription of the hPTH gene.

Animals↗
PubMed1991

Random screening of promoters from Escherichia coli and classification based on the promoter strength.

Five hundred fifty DNA fragments 100-500 base pairs in length were cloned from total chromosomal DNA of Escherichia coli, each capable of promoting the synthesis of beta-lactamase when inserted upstream of the ampC structural gene without its own promoter in a promoter-probe plasmid. All clones in this library of putative promoters were classified based on the level of resistance to ampicillin, which ranged from 10 to more than 1,500 micrograms/ml. Most of the higher levels of drug resistance (more than 1,000 micrograms/ml) were due not only to an increase in gene expression but also to an increase in plasmid copy number. The DNA fragments which produced the highest level of drug resistance all mapped at 5.7 min on the E. coli chromosome and shared the same nucleotide sequence. In these fragments, a strong promoter was found, which carries an up stream AT-rich sequence in addition to -35 and -10 signals of the promoter consensus.

Ampicillin Resistance↗
PubMed1994

Promoter screening from Pseudomonas species by a promoter probe transposon and its structure.

By use of the promoter probe transposon Tn5-B21, two promoter fragments were isolated. One promoter (822 bp) (GC = 63.5%) isolated from P. putida loses all of its promoter activity by exonuclease or restriction enzyme deletion. Another promoter (264 bp) (GC = 49.2%) isolated from P. fluorescens could be shortened to 154 bp by exonuclease deletion without any effect on its promoter activity in several Pseudomonas species.

DNA Transposable Elements↗