Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of expression of the human beta-1,2-N-acetylglucosaminyltransferase II gene (MGAT2) by Ets transcription factors.

ABSTRACT: Oncogenic transformation of fibroblasts by the src oncogene has long been known to cause an increase in the size of cell-surface protein-bound oligosaccharides, owing primarily to increased N-glycan branching mediated by increased beta-1,6-N-acetylglucosaminyltransferase V (GnT V) activity. The src-responsive element of the GnT V promoter was localized to Ets-binding sites and the promoter was transcriptionally stimulated by both ets-1 and ets-2 expression [Buckhaults, Chen, Fregien and Pierce (1997) J. Biol. Chem. 272, 19575-19581; Kang, Saito, Ihara, Miyoshi, Koyama, Sheng and Taniguchi (1996) J. Biol. Chem. 271, 26706-26712]. Because GnT V action requires the prior action of beta-1,2-N-acetylglucosaminyltransferase II (GnT II) and the human GnT II promoter contains four putative Ets-binding sites [Chen, Zhou, Tan and Schachter (1998) Glycoconj. J. 15, 301-308], GnT II might also be under oncogenic control via Ets transcription factors. We now report that co-transfection into HepG2 or COS-1 cells of either ets-1 or ets-2 expression plasmids together with chimaeric GnT II promoter-chloramphenicol acetyltransferase plasmids results in a 2-4-fold stimulation of promoter activity. Mobility-shift assays and South-Western blots localized the functional Ets-binding site to one of the four putative sites on the GnT II promoter. The GnT II promoter, unlike the GnT V promoter, is not activated by either src or neu. Therefore although both promoters are stimulated by a member of the Ets family of transcription factors, the functional role of this Ets transcriptional control seems to be different for the two genes.

SUBMITTER: Zhang W

PROVIDER: S-EPMC1220984 | biostudies-other | 2000 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors.

Project description:Vascular development begins when mesodermal cells differentiate into endothelial cells, which then form primitive vessels. It has been hypothesized that endothelial-specific gene expression may be regulated combinatorially, but the transcriptional mechanisms governing specificity in vascular gene expression remain incompletely understood. Here, we identify a 44 bp transcriptional enhancer that is sufficient to direct expression specifically and exclusively to the developing vascular endothelium. This enhancer is regulated by a composite cis-acting element, the FOX:ETS motif, which is bound and synergistically activated by Forkhead and Ets transcription factors. We demonstrate that coexpression of the Forkhead protein FoxC2 and the Ets protein Etv2 induces ectopic expression of vascular genes in Xenopus embryos, and that combinatorial knockdown of the orthologous genes in zebrafish embryos disrupts vascular development. Finally, we show that FOX:ETS motifs are present in many known endothelial-specific enhancers and that this motif is an efficient predictor of endothelial enhancers in the human genome.

| S-EPMC2782666 | biostudies-literature

Regulation of DYT1 gene expression by the Ets family of transcription factors.

Project description:The DYT1 gene encodes for torsinA, a protein with widespread tissue distribution, involved in early onset dystonia (EOD). Numerous studies have focused on torsinA function but no information is available on its transcriptional regulation. We cloned mouse and human 5'-upstream DYT1 DNA fragments, exhibiting high transcriptional activity, as well as tissue specificity. We identified a proximal minimal DYT1 promoter within -141 bp for mouse and -191 bp for human with respect to the ATG codon. Primer extension analysis indicated multiple transcription start sites. In silico analysis of approximately 500 bp 5'-upstream DYT1 fragment demonstrated lack of a classical TATA or CAAT box and the presence of a highly conserved direct repeat of two Ets binding cores within -86 bp to -77 bp and -78 bp to -69 bp of the mouse and human DYT1 gene, respectively. A single or a two base nucleotide alteration within the downstream Ets core resulted in approximately 90% (mouse) or 45-60% (human) drop in activity. Interestingly, a 3-bp distance increase between the two Ets cores dramatically decreased transcriptional activity which was partially restored when the distance was increased up to 10 bp. Ets-like dominant negatives confirmed the Ets factors as DYT1 transcriptional activators.

| S-EPMC2668265 | biostudies-literature

Function and regulation of the PEA3 subfamily of ETS transcription factors in cancer.

Project description:The PEA3 subfamily is a subgroup of the E26 transformation-specific (ETS) family. Its members, ETV1, ETV4, and ETV5, have been found to be overexpressed in multiple cancers. The deregulation of ETV1, ETV4, and ETV5 induces cell growth, invasion, and migration in various tumor cells, leading to tumor progression, metastasis, and drug resistance. Therefore, exploring drugs or therapeutic targets that target the PEA3 subfamily may contribute to the clinical treatment of tumor patients. In this review, we introduce the structures and functions of the PEA3 subfamily members, systematically review their main roles in various tumor cells, analyze their prognostic and diagnostic value, and, finally, introduce several molecular targets and therapeutic drugs targeting ETV1, ETV4, and ETV5. We conclude that targeting a series of upstream regulators and downstream target genes of the PEA3 subfamily may be an effective strategy for the treatment of ETV1/ETV4/ETV5-overexpressing tumors.

| S-EPMC7642666 | biostudies-literature

Regulation of PLPP3 gene expression by NF-?B family transcription factors.

Project description:Lipid phosphate phosphatase 3 (LPP3), encoded by the PLPP3 gene, is an integral membrane enzyme that dephosphorylates phosphate esters of glycero- and sphingophospholipids. Cell surface LPP3 can terminate the signaling actions of bioactive lysophosphatidic acid (LPA) and sphingosine 1 phosphate, which likely explains its role in developmental angiogenesis, vascular injury responses, and cell migration. Heritable variants in the final intron PLPP3 associate with interindividual variability in coronary artery disease risk that may result from disruption of enhancer sequences that normally act in cis to increase expression of the gene. However, the mechanisms regulating PLPP3 expression are not well understood. We show that the human PLPP3 promoter contains three functional NF-?B response elements. All of these are required for maximal induction of PLPP3 promoter activity in reporter assays. The identified sequences recruit RelA and RelB components of the NF-?B transcription complex to chromatin, and these transcription factors bind to the identified target sequences in two different cell types. LPA promotes binding of Rel family transcription factors to the PLPP3 promoter and increases PLPP3 gene expression through mechanisms that are attenuated by an NF-?B inhibitor, LPA receptor antagonists, and inhibitors of phosphoinositide 3 kinase. These findings indicate that up-regulation of PLPP3 during inflammation and atherosclerosis results from canonical activation of the NF-?B signaling cascade to increase PLPP3 expression through nuclear import and binding of RelA and RelB transcription factors to the PLPP3 promoter and suggest a mechanism by which the LPP3 substrate, LPA, can regulate PLPP3 expression.

| S-EPMC6755815 | biostudies-literature

Gene Regulatory Network of ETS Domain Transcription Factors in Different Stages of Glioma.

Project description:The ETS domain family of transcription factors is involved in a number of biological processes, and is commonly misregulated in various forms of cancer. Using microarray datasets from patients with different grades of glioma, we have analyzed the expression profiles of various ETS genes, and have identified ETV1, ELK3, ETV4, ELF4, and ETV6 as novel biomarkers for the identification of different glioma grades. We have further analyzed the gene regulatory networks of ETS transcription factors and compared them to previous microarray studies, where Elk-1-VP16 or PEA3-VP16 were overexpressed in neuroblastoma cell lines, and we identify unique and common regulatory networks for these ETS proteins.

| S-EPMC7922321 | biostudies-literature

The PEA3 subfamily of Ets transcription factors synergizes with beta-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors.

Project description:The matrix metalloproteinase matrilysin (MMP-7) is expressed in the tumor cells of a majority of mouse intestinal and human colonic adenomas. We showed previously that matrilysin is a target gene of beta-catenin-Tcf, the transcription factor complex whose activity is thought to play a crucial role in the initiation of intestinal tumorigenesis. Here we report that overexpression of a stable mutant form of beta-catenin alone was not sufficient to effect expression of luciferase from a matrilysin promoter-luciferase reporter plasmid. However, cotransfection of the reporter with an expression vector encoding the PEA3 Ets transcription factor, or its close relatives ER81 and ERM, increased luciferase expression and rendered the promoter responsive to beta-catenin-LEF-1 as well as to the AP-1 protein c-Jun. Other Ets proteins could not substitute for the PEA3 subfamily. Luciferase activity was induced up to 250-fold when PEA3, c-Jun, beta-catenin, and LEF-1 were coexpressed. This combination of transcription factors was also sufficient to induce expression of the endogenous matrilysin gene. Furthermore, all matrilysin-expressing benign intestinal tumors of the Min mouse expressed a member of the PEA3 subfamily, as did all human colon tumor cell lines examined. These data suggest that the expression of members of the PEA3 subfamily, in conjunction with the accumulation of beta-catenin in these tumors, leads to coordinate upregulation of matrilysin gene transcription, contributing to gastrointestinal tumorigenesis.

| S-EPMC99589 | biostudies-literature

Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors.

Project description:The construction of increasingly sophisticated synthetic biological circuits is dependent on the development of extensible tools capable of providing specific control of gene expression in eukaryotic cells. Here, we describe a new class of synthetic transcription factors that activate gene expression in response to extracellular chemical stimuli. These inducible activators consist of customizable transcription activator-like effector (TALE) proteins combined with steroid hormone receptor ligand-binding domains. We demonstrate that these ligand-responsive TALE transcription factors allow for tunable and conditional control of gene activation and can be used to regulate the expression of endogenous genes in human cells. Since TALEs can be designed to recognize any contiguous DNA sequence, the conditional gene regulatory system described herein will enable the design of advanced synthetic gene networks.

| S-EPMC4097969 | biostudies-literature

Signatures of DNA target selectivity by ETS transcription factors.

Project description:The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation.

| S-EPMC5501379 | biostudies-literature

Collaborative repressive action of the antagonistic ETS transcription factors Pointed and Yan fine-tunes gene expression to confer robustness in Drosophila.

Project description:The acquisition of cellular identity during development depends on precise spatiotemporal regulation of gene expression, with combinatorial interactions between transcription factors, accessory proteins and the basal transcription machinery together translating complex signaling inputs into appropriate gene expression outputs. The opposing repressive and activating inputs of the Drosophila ETS family transcription factors Yan and Pointed orchestrate numerous cell fate transitions downstream of receptor tyrosine kinase signaling, providing one of the premier systems for studying this process. Current models describe the differentiative transition as a switch from Yan-mediated repression to Pointed-mediated activation of common target genes. We describe here a new layer of regulation whereby Yan and Pointed co-occupy regulatory elements to repress gene expression in a coordinated manner, with Pointed being unexpectedly required for the genome-wide occupancy of both Yan and the co-repressor Groucho. Using even skipped as a test-case, synergistic genetic interactions between Pointed, Groucho, Yan and components of the RNA polymerase II pausing machinery suggest that Pointed integrates multiple scales of repressive regulation to confer robustness. We speculate that this mechanism may be used broadly to fine-tune the expression of many genes crucial for development.

| S-EPMC6053666 | biostudies-literature

Critical role for Ets, AP-1 and GATA-like transcription factors in regulating mouse Toll-like receptor 4 (Tlr4) gene expression.

Project description:TLR4 (Toll-like receptor 4) is essential for sensing the endotoxin of Gram-negative bacteria. Mutations or deletion of the TLR4 gene in humans or mice have been associated with altered predisposition to or outcome of Gram-negative sepsis. In the present work, we studied the expression and regulation of the Tlr4 gene of mouse. In vivo, TLR4 levels were higher in macrophages compared with B, T or natural killer cells. High basal TLR4 promoter activity was observed in RAW 264.7, J774 and P388D1 macrophages transfected with a TLR4 promoter reporter vector. Analysis of truncated and mutated promoter constructs identified several positive [two Ets (E twenty-six) and one AP-1 (activator protein-1) sites] and negative (a GATA-like site and an octamer site) regulatory elements within 350 bp upstream of the transcriptional start site. The myeloid and B-cell-specific transcription factor PU.1 bound to the proximal Ets site. In contrast, none among PU.1, Ets-1, Ets-2 and Elk-1, but possibly one member of the ESE (epithelium-specific Ets) subfamily of Ets transcription factors, bound to the distal Ets site, which was indispensable for Tlr4 gene transcription. Endotoxin did not affect macrophage TLR4 promoter activity, but it decreased TLR4 steady-state mRNA levels by increasing the turnover of TLR4 transcripts. TLR4 expression was modestly altered by other pro- and anti-inflammatory stimuli, except for PMA plus ionomycin which strongly increased promoter activity and TLR4 mRNA levels. The mouse and human TLR4 genes were highly conserved. Yet, notable differences exist with respect to the elements implicated in gene regulation, which may account for species differences in terms of tissue expression and modulation by microbial and inflammatory stimuli.

| S-EPMC1134963 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data