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Results for “regulatory element transcripts”

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At least 919 records · Page 51Linked to original sources
PubMed1990

Identification of a TFIIIA binding site on the 5' flanking region of the TFIIIA gene.

Xenopus transcription factor IIIA (TFIIIA) regulates 5S ribosomal RNA gene transcription in a positive manner by binding to the internal control region (ICR) of the 5S RNA gene. The present study reports the identification of a TFIIIA binding site on the 5' flanking region of the Xenopus laevis gene that codes for the synthesis of this transcription factor. This TFIIIA binding site (deduced from TFIIIA-dependent alterations in DNase I protection patterns) extends on the 5' flanking region from about nucleotide -326 to -264 on the non-coding strand and from -331 to -271 on the coding strand. The affinity of TFIIIA for the 5' flanking region of its own gene is less than that for the 5S RNA gene but within the same order of magnitude. A sequence similarity between this newly identified binding site and the 5S gene ICR is the presence of purine-rich tracts. EDTA chelation of TFIIIA inhibits binding to this 5' flanking element indicating, as with the 5S RNA gene, zinc is required for DNA binding specificity. When TFIIIA is bound to 5S RNA in the 7S particle, the protein does not bind to this 5' flanking region, an observation similar to that observed with binding to the 5S RNA gene. These results indicate TFIIIA is using similar nucleic acid binding domain(s) for interaction with the 5S gene, 5S RNA, and the 5' flanking region of its own gene. This upstream DNA region to which TFIIIA binds has been previously shown to contain a negative and a positive regulatory element for transcription of the TFIIIA gene (Scotto, K.W., Kaulen, H., and Roeder, R.G., 1989, Genes & Develop. 3, 651-662). The present results indicate TFIIIA binds to the negative control element located at -306 to -289 and possibly interacts/interferes with another transcription factor which binds to the positive control element extending from -271 to -253.

Animals↗
PubMed2001

Cholecystokinin gene transcription: promoter elements, transcription factors and signaling pathways.

Cholecystokinin (CCK) is a neuropeptide expressed in the small intestine and in the central and peripheral nervous system. CCK gene expression is both spatially and temporally regulated. In neurons CCK production is increased by growth factors, cyclic adenosine 3', 5'-monophosphate (cAMP), dopamine, estrogen, and injury situations, while intestinal CCK expression is mainly regulated by food intake. The function of the proximal CCK promoter has been examined by transfection of human CCK-CAT reporter constructs in cultured cells, DNase I footprinting and gel shift assays. These studies have led to the identification of regulatory elements and transcription factors important for basal and stimulated gene expression and depicted the signaling pathways involved in growth factor and cAMP induced CCK transcription. The review outlines the current knowledge of the regulation of CCK transcription and describes the role of putative transcription factors in tissue-specific CCK gene expression.

Animals↗
PubMed2006

Regulation of RNA-polymerase-II-dependent transcription by N-WASP and its nuclear-binding partners.

The presence of actin in the nucleus has been well established, and several studies have implicated nuclear actin in transcriptional regulation. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is a member of the WASP family of proteins; these proteins function in the cytoplasm as key regulators of cortical actin filament. Interestingly, N-WASP has also been observed in the nucleus. However, a potential nuclear function for N-WASP has not been established. Here, we report the identification of nuclear N-WASP within a large nuclear-protein complex containing PSF-NonO (polypyrimidine-tract-binding-protein-associated splicing factor-non-Pou-domain octamer-binding protein/p54(nrb)), nuclear actin and RNA polymerase II. The PSF-NonO complex is involved in the regulation of many cellular processes, such as transcription, RNA processing, DNA unwinding and repair. We demonstrate that the interaction of N-WASP with the PSF-NonO complex can couple N-WASP with RNA polymerase II to regulate transcription. We also provide evidence that the potential function of N-WASP in promoting polymerization of nuclear actins has an important role in this process. Based on these results, we propose a nuclear function for N-WASP in transcriptional regulation.

Actin Cytoskeleton↗
PubMed1992

Novel DNA-binding proteins regulate intestine-specific transcription of the sucrase-isomaltase gene.

Sucrase-isomaltase (SI) is an enterocyte-specific gene which exhibits a complex pattern of expression during intestinal development and in the adult intestinal mucosa. In the studies described in this report, we demonstrate that enterocyte-specific transcription of the SI gene is regulated by an evolutionarily conserved promoter that extends approximately 180 bp upstream of the transcription start site. DNase I footprint analysis allowed the identification of three nuclear protein-binding sites within the SI promoter (SIF1, SIF2, and SIF3 [SI footprint]), each of which acted as a positive regulatory element for transcription in intestinal cell lines. SIF1 was shown to bind nuclear protein complexes present in primary mouse small intestinal cell and in an intestinal cell line (Caco-2). However, SIF1-binding proteins were absent in a variety of other epithelial and nonepithelial cells. In vitro mutagenesis experiments demonstrated that the SIF1 site is required for high-level promoter activity in intestinal cells. The SIF3 element formed prominent binding complexes with intestinal and liver nuclear extracts, whereas nuclear proteins from other epithelial and nonepithelial cells formed weaker complexes of different mobilities. The SIF2 element bound nuclear proteins in a pattern similar to that of SIF3, and cross-competition studies suggested that SIF2 and SIF3 may bind the same nuclear proteins. Taken together, these data have allowed the identification of novel DNA-binding proteins that play an important role in regulating intestine-specific transcription of the SI gene.

Animals↗
PubMed1994

Cell-specific expression of the macrophage scavenger receptor gene is dependent on PU.1 and a composite AP-1/ets motif.

The type I and II scavenger receptors (SRs) are highly restricted to cells of monocyte origin and become maximally expressed during the process of monocyte-to-macrophage differentiation. In this report, we present evidence that SR genomic sequences from -245 to +46 bp relative to the major transcriptional start site were sufficient to confer preferential expression of a reporter gene to cells of monocyte and macrophage origin. This profile of expression resulted from the combinatorial actions of multiple positive and negative regulatory elements. Positive transcriptional control was primarily determined by two elements, located 181 and 46 bp upstream of the major transcriptional start site. Transcriptional control via the -181 element was mediated by PU.1/Spi-1, a macrophage and B-cell-specific transcription factor that is a member of the ets domain gene family. Intriguingly, the -181 element represented a relatively low-affinity binding site for Spi-B, a closely related member of the ets domain family that has been shown to bind with relatively high affinity to other PU.1/Spi-1 binding sites. These observations support the idea that PU.1/Spi-1 and Spi-B regulate overlapping but nonidentical sets of genes. The -46 element represented a composite binding site for a distinct set of ets domain proteins that were preferentially expressed in monocyte and macrophage cell lines and that formed ternary complexes with members of the AP-1 gene family. In concert, these observations suggest a model for how interactions between cell-specific and more generally expressed transcription factors function to dictate the appropriate temporal and cell-specific patterns of SR expression during the process of macrophage differentiation.

Animals↗
PubMed1993

Nerve growth factor induces transcription of NGFIA through complex regulatory elements that are also sensitive to serum and phorbol 12-myristate 13-acetate.

The expression of NGFIA (also known as egr1, zif268, TIS8, krox24, and d2) is rapidly and transiently increased by nerve growth factor (NGF) in PC12 cells. The 5'-region of this gene includes four serum response elements (SREs), a cAMP-like response element, an AP1-like response element, and an SP1-binding site. From deletion analysis of chloramphenicol acetyltransferase reporter constructs, we have established that the first 106 basepairs 5' of the transcriptional start site are sufficient for induction of NGFIA by NGF in PC12 cells; deletion beyond this point results in dramatically reduced induction of the gene. Using defined mutations in the NGFIA promoter and NGFIA-thymidine kinase hybrid promoters, we have defined three elements (SRE1, SRE2, and AP1-like) in the first 106 basepairs of upstream DNA, each of which contributes to induction of NGFIA by NGF. Cooperation by two of these elements (i.e. the two SREs or one SRE and the AP1-like element) is sufficient to confer transcriptional induction by NGF, but the combination of all three elements increased induction by NGF more effectively than a pair of elements. This suggests that the response of NGFIA to NGF is mediated by a cis-acting sequence that is composed of at least three distinct elements. An oligonucleotide composed of SRE1 and SRE2 that can confer the ability for NGF induction to heterologous promoter constructs complexes with proteins in PC12 cell nuclear extracts, but the protein-DNA complexes do not appear to be altered by NGF treatment, as measured by DNA mobility shift assays. We have also established that the regulatory region of NGFIA that mediates NGF induction also mediates the induction by serum and phorbol 12-myristate 13-acetate, suggesting that multiple signal transduction pathways must converge on these sequences to regulate the expression of this gene.

Animals↗
PubMed2004

Genetic variants in human sterol regulatory element binding protein-1c in syndromes of severe insulin resistance and type 2 diabetes.

The transcription factor sterol regulatory element binding protein (SREBP)-1c is intimately involved in the regulation of lipid and glucose metabolism. To investigate whether mutations in this gene might contribute to insulin resistance, we screened the exons encoding the aminoterminal transcriptional activation domain in a cohort of 85 unrelated human subjects with severe insulin resistance. Two missense mutations (P87L and P416A) were found in single affected patients but not in 47 control subjects. However, these variants were indistinguishable from the wild-type in their ability to bind DNA or to transactivate an SREBP-1 responsive promoter construct. We also identified a common intronic single nucleotide polymorphism (C/T) located between exon 18c and 19c. In a case-control study of 517 U.K. Caucasian case subjects and 517 age- and sex-matched control subjects, the T-allele at this locus was significantly associated with type 2 diabetes in men (odds ratio = 1.42 [1.11-1.82], P = 0.005) but not women. In a separate population-based study of 1,100 Caucasians, carriers of the T-allele showed significantly higher levels of total and LDL cholesterol (P < 0.05) compared with wild-type individuals. In summary, we have conducted the first study of the SREBP-1c gene as a candidate for human insulin resistance. Although the rare mutations identified were functionally silent in the assays used, we obtained some evidence, which requires conformation in other populations, that a common variant in the SREBP-1c gene might influence diabetes risk and plasma cholesterol level.

Base Sequence↗
PubMed2005

Active repression of IFN regulatory factor-1-mediated transactivation by IFN regulatory factor-4.

IFN regulatory factor-4 (IRF-4) is a transcription factor that is involved in the development and the functions of lymphocytes, macrophages and dendritic cells. Despite their critical roles in immune system regulation, the target genes controlled by IRF-4 are poorly understood. In this study, we determined the consensus DNA-binding sequences preferred for IRF-4 by in vitro binding site selections. IRF-4 preferentially bound to the sequences containing tandem repeats of 5'-GAAA-3', flanked by CpC, in most cases. IRF-4 repressed the promoter bearing tandem copies of the selected binding sequence, while IRF-1 activated the same constructs. Interestingly, the IRF-1-dependent transactivation is inhibited in the presence of IRF-4, but not IRF-2. A series of deletion mutants of IRF-4 revealed that its DNA-binding domain was necessary and sufficient to antagonize the IRF-1-dependent transactivation. This dominant negative action of IRF-4 over IRF-1 was also observed in a natural promoter context, such as the TRAIL gene. These results indicate that IRF-4 acts as a natural antagonist against IRF-1 in immune cells.

Apoptosis Regulatory Proteins↗
PubMed2006

The UBX-regulated network in the haltere imaginal disc of D. melanogaster.

Hox proteins have been proposed to act at multiple levels within regulatory hierarchies and to directly control the expression of a plethora of target genes. However, for any specific Hox protein or tissue, very few direct in vivo-regulated target genes have been identified. Here, we have identified target genes of the Hox protein Ultrabithorax (UBX), which modifies the genetic regulatory network of the wing to generate the haltere, a modified hindwing. We used whole-genome microarrays and custom arrays including all predicted transcription factors and signaling molecules in the Drosophila melanogaster genome to identify differentially expressed genes in wing and haltere imaginal discs. To elucidate the regulation of selected genes in more detail, we isolated cis-regulatory elements (CREs) for genes that were specifically expressed in either the wing disc or haltere disc. We demonstrate that UBX binds directly to sites in one element, and these sites are critical for activation in the haltere disc. These results indicate that haltere and metathoracic segment morphology is not achieved merely by turning off the wing and mesothoracic development programs, but rather specific genes must also be activated to form these structures. The evolution of haltere morphology involved changes in UBX-regulated target genes, both positive and negative, throughout the wing genetic regulatory network.

Animals↗
PubMed1992

A transcriptional silencer downstream of the promoter in the osmotically controlled proU operon of Salmonella typhimurium.

The proU operon of Salmonella typhimurium is induced by conditions of high osmolality. The cis-acting sequences that mediate osmotic control of transcription were characterized by deletion analysis. The nucleotide sequence between -60 and +274 (relative to the transcription start point) is sufficient for normal osmotic control. Deletions that removed sequences upstream of position +274 but left the promoter intact resulted in greatly increased expression from the proU promoter in the absence of osmotic stress. Thus, the transcription control region of the proU operon consists of two discrete components: (i) the promoter and (ii) a negatively acting site that overlaps the coding sequence of the first structural gene of the operon, proV. That this negative regulatory element is a transcriptional terminator or mRNA processing site was ruled out. Our results suggest that the negative regulatory element behaves as a transcriptional silencer that inhibits transcription initiation at the proU promoter in medium of low osmolality by some action at a distance. We propose several possible mechanisms for the function of this regulatory site.

Base Sequence↗
PubMed2004

Finb, a multiple zinc finger protein, represses transcription of the human angiotensinogen gene.

We previously identified a regulatory element at the 3'-downstream region of the human angiotensinogen (hANG) gene. Using this element as a probe by the Southwestern screening, we isolated a cDNA clone, encoding Finb, a transcriptional activator with multiple zinc finger domains. The N-terminal zinc finger domain of Finb bound to the GGATGG sequence within the regulatory element. Unexpectedly, Finb repressed transcription dependent on the regulatory element. Inspection of the 5'-flanking region in the hANG promoter identified the GGATGG-like elements, which prompted us to examine the effect of Finb on the hANG promoter activity. We also found the two Finb binding elements in the 5'-flanking region of the hANG gene by the gel shift assay, both of which were necessary for transcriptional repression of the hANG promoter. These findings suggest that Finb functions as a sequence-specific transcriptional repressor of the hANG gene.

Angiotensinogen↗
PubMed2006

Functional characterization of the promoter for the mouse SPTLC2 gene, which encodes subunit 2 of serine palmitoyltransferase.

A series of luciferase reporter constructs was prepared from a 1035-bp fragment of mouse genomic DNA flanking the 5'-coding sequence for the SPTLC2 subunit of serine palmitoyltransferase, the initial enzyme of de novo sphingolipid biosynthesis. The full-length DNA fragment promoted strong reporter gene expression in NIH3T3 cells while deletion and site-directed mutagenesis indicated that the proximal 335 bp contain initiator and downstream promoter elements, two proximal GC boxes that appear to stimulate transcription in a cooperative manner, and several additional elements whose activity cannot be accounted for by known factor binding sites. These findings provide insight into the control mechanisms for transcription of mammalian SPTLC2.

Animals↗
PubMed2025

Through the lens of bioenergy crops: advances, bottlenecks, and promises of plant engineering.

Advances in engineering of bioenergy crops were driven over the past years by adapting technological breakthroughs and accelerating conventional applications but also exposed intriguing challenges. New tools revealed rich interconnectivity in the exponentially growing and dynamic 'big' omics data' of metabolomes, transcriptomes, and genomes at previously inaccessible magnitude (global, cross-species, meta-) and resolution (single cell). Insights enabled fresh hypotheses and stimulated disciplines such as functional genomics with discovery of broad regulatory networks and their determinants, that is, DNA parts, including promoters, regulatory elements, and transcription factors. Their rational design, assembly into increasingly complex blueprints, and installation into diverse chassis is an existing frontier that may benefit from emerging technologies to address bottlenecks. Interweaving nature-inspired to fully synthetic parts has already allowed building of fine-tuned regulatory circuits, or new-to-nature metabolic routes insulated from the biological context of the chassis species. Similarly, developments and the evolving need for unifying principles in plant transformation and species-agnostic technologies highlight future opportunities for engineering the next generation of bioenergy plants.

Crops, Agricultural↗
PubMed2005

A basic helix-loop-helix transcription factor in Arabidopsis, MYC2, acts as a repressor of blue light-mediated photomorphogenic growth.

The crosstalk of light signaling pathways with other signaling cascades has just started to be revealed. Here, we report the identification and functional characterization of a Z-box binding factor (ZBF1) in light signaling pathways. Arabidopsis thaliana ZBF1 encodes AtMYC2/JIN1, a basic helix-loop-helix transcription factor, which has recently been shown to be involved in abscisic acid (ABA), jasmonic acid (JA), and jasmonate-ethylene signaling pathways. We demonstrate that AtMYC2 interacts with the Z- and G-box light-responsive elements of minimal light-regulated promoters. AtMYC2 is expressed in various light-grown seedlings, including in red, far red, and blue light. Genetic analyses suggest that AtMYC2 acts as a negative regulator of blue light-mediated photomorphogenic growth and blue and far-red-light-regulated gene expression; however, it functions as a positive regulator of lateral root formation. Our results further demonstrate that atmyc2 mutants have compromised sensitivity to ABA- and JA-mediated responses. Taken together, these results demonstrate that AtMYC2 is a common transcription factor of light, ABA, and JA signaling pathways in Arabidopsis.

Abscisic Acid↗
PubMed2006

Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene.

The zinc finger transcription factor Osterix (Osx) regulates bone formation and osteoblast differentiation in vitro and in vivo. We investigated the transcriptional mechanisms underlying the mouse Osx expression by isolating and characterizing its 5' upstream region. We performed 5' RACE on mRNA isolated from murine chondroprogenitor cells and determined a cap site of Osx approximately -99 nucleotides upstream of the initiation codon. Sequence analysis of this TATA-less promoter shows several putative response elements for Sox9, VDRE, Runx and Sp1. Transfection of the Osx promoter driving the luciferase reporter gene into C3H10T1/2 and ATDC5 cells shows a strong basal promoter activity between 565 bp and 2 kb. Deletion mutant analyses show that the most proximal 852 kb of the Osx promoter contains the highest activating domains, while strong repressive domains were identified between 1.8 and 2 kb. Over-expression experiments indicate that Runx2 significantly transactivates the Osx promoter by at least 2 fold indicating that Osx is downstream of Runx2 in mesenchymal cells. This up-regulation was abrogated when the Runx2 responsive element on the Osx promoter was mutated. Finally, we show that Runx2 specifically binds to this DNA element in the Osx promoter. Thus our results show for the first time Osx transcriptional regulation through the bone and cartilage related transcription factor Runx2.

Alternative Splicing↗
PubMed1998

Influence of FIS on the transcription from closely spaced and non-overlapping divergent promoters for an aminoacyl-tRNA synthetase gene (gltX) and a tRNA operon (valU) in Escherichia coli.

The gltX gene, encoding the glutamyl-tRNA synthetase (GluRS), and the valU operon, whose transcripts contain three tRNAVal/UAC and one tRNALys/UUU, are adjacent and divergently transcribed. It is the only known case of adjacent genes encoding an aminoacyl-tRNA synthetase and a tRNA precursor in Escherichia coli. The gltX promoters (P1, P2 and P3) direct the synthesis of transcripts non-overlapping with and divergent from the one initiated at the valU promoter. We report that their promoter region (250 bp) contains three binding sites for the factor for inversion stimulation (FIS), centred at positions -71, -91 and -112 from the valU transcription initiation site, and that the destruction of any of these sites does not prevent the binding of FIS to the others. As FIS is one of the major positive regulators of stable RNA operons, we have studied its role on gltX and valU transcription. FIS stimulates valU transcription in vitro and about twofold in vivo during steady-state exponential growth. In contrast, gltX transcription is repressed by the presence of FIS in vitro and about twofold in vivo during growth acceleration when a decrease in GluRS concentration was observed. Under all conditions tested, most of the gltX transcripts start at the P3 promoter. Nested deletions of this regulatory region reveal that the FIS-dependent repression of the gltX-P3 promoter is abolished after the removal of the valU promoter, and is not altered by the additional removal of the FIS binding sites; moreover, in vivo transcription from gltX-P1 and/or gltX-P2 present on some of these regulatory region variants is modulated by the nature of the upstream region by FIS and is sometimes stronger than that from gltX-P3. These results show that the strength and the site of gltX transcription initiation are influenced by the upstream region up to and including the valU promoter; furthermore, they indicate that although these adjacent genes are involved in the first step of protein biosynthesis and share cis and trans regulatory elements, their transcription is non-co-ordinate.

Amino Acyl-tRNA Synthetases↗
PubMed2005

Inflammation-responsive transcription factors SAF-1 and c-Jun/c-Fos promote canine MMP-1 gene expression.

Matrix metalloproteinase-1 (MMP-1) has been implicated in the pathogenesis of osteoarthritis (OA) due to its ability to degrade extracellular matrix component of the joint cartilage tissue that cushions the bone from frictional damage. Canine hip dysplasia, a developmental orthopedic disease which results in arthritic condition as is seen in human OA is an excellent system to study the involvement of MMP-1 in the pathogenesis of OA. To date, however, no report is available regarding canine MMP-1 promoter and the regulatory mechanism by which increased synthesis of MMP-1 protein might be regulated. To gain an insight, we have investigated the promoter region of canine MMP-1. MMP-1 synthesis in the resident cells of arthritic joints is regulated via two major cytokines, IL-1beta and TNF-alpha. By using a series of progressively deleted reporter constructs, multiple cytokine-responsive elements were identified in the proximal promoter region of canine MMP-1. These include DNA-binding elements of AP-1 and SAF-1 transcription factors. Mutation of AP-1 or SAF-1 element resulted in marked reduction in the cytokine responsiveness of MMP-1 promoter. We show that AP-1 and SAF-1 DNA-binding activities are increased in cytokine-stimulated cells as well as in osteoarthritic cartilage tissues. In correlation, immunohistochemical analysis indicated higher levels of MMP-1, SAF-1 and AP-1 proteins in osteoarthritic but not in the normal cartilage tissue. These results show that induction and activation of AP-1 and SAF-1 transcription factors are involved in the regulation of MMP-1 expression in the chondrocytes which could be used as therapeutic targets to combat pathogenesis of OA.

Animals↗