Hormonal regulation of gene expression: regulation of growth hormone gene transcription by growth hormone releasing factor.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Gene Expression Regulation”
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.
The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression.
Regulation of NF-kappaB transactivation function is controlled at several levels, including interactions with coactivator proteins. Here we show that the transactivation function of NF-kappaB is also regulated through interaction of the p65 (RelA) subunit with histone deacetylase (HDAC) corepressor proteins. Our results show that inhibition of HDAC activity with trichostatin A (TSA) results in an increase in both basal and induced expression of an integrated NF-kappaB-dependent reporter gene. Chromatin immunoprecipitation (ChIP) assays show that TSA treatment causes hyperacetylation of the wild-type integrated NF-kappaB-dependent reporter but not of a mutant version in which the NF-kappaB binding sites were mutated. Expression of HDAC1 and HDAC2 repressed tumor necrosis factor (TNF)-induced NF-kappaB-dependent gene expression. Consistent with this, we show that HDAC1 and HDAC2 target NF-kappaB through a direct association of HDAC1 with the Rel homology domain of p65. HDAC2 does not interact with NF-kappaB directly but can regulate NF-kappaB activity through its association with HDAC1. Finally, we show that inhibition of HDAC activity with TSA causes an increase in both basal and TNF-induced expression of the NF-kappaB-regulated interleukin-8 (IL-8) gene. Similar to the wild-type integrated NF-kappaB-dependent reporter, ChIP assays showed that TSA treatment resulted in hyperacetylation of the IL-8 promoter. These data indicate that the transactivation function of NF-kappaB is regulated in part through its association with HDAC corepressor proteins. Moreover, it suggests that the association of NF-kappaB with the HDAC1 and HDAC2 corepressor proteins functions to repress expression of NF-kappaB-regulated genes as well as to control the induced level of expression of these genes.
3T3 Cells↗
Gene expression regulation and cancer.
Gene expression is mostly controlled at the level of the transcription initiation. The transcription control regions of protein-encoding genes include: the core promoter, where RNA polymerase II binds, the proximal and distal promoter, responsible for gene expression regulation, and the enhancers and silencers. Chromatin represents an additional level of regulation of gene expression. The switching between inactive and active chromatin is closely related to the activity of histone-modifying enzymes and chromatin-remodelling complexes. Transcriptional activation of a gene requires the binding of specific transcription factors to regulatory DNA elements, the opening of the chromatin, the binding of Mediator, and the assembly of the preinitiation complex with RNA polymerase and RNA synthesis initiation. Transcription factors ultimately transduce the proliferation signals elicited by growth factors. Moreover, many human oncogenes encode for transcription factors, and some of them are prevalent in particular neoplasias (e.g., MYC, MLL, PML-RARa). Also, some of the most prominent tumor suppressors (e.g. p53) are transcription factors.
Animals↗
Regulating gene expression in transgenic animals.
Regardless of the field of application, the raison d'etre of transgenic animals is to study gene regulation and function. With increasing frequency, mammalian genes are being isolated with no concomitant knowledge of their function. The human genome mapping initiative will undoubtedly produce a cornucopia of such genes. While the merit of taking a transgenic route to study genes of unknown function is axiomatic, the choices of strategies for gene regulation in vivo may not be fully appreciated. This review will address two main points: first, the targeted and regulated expression of genes, and second, the structural and functional ablation of genes.
Animals↗
CAGER: classification analysis of gene expression regulation using multiple information sources.
BACKGROUND: Many classification approaches have been applied to analyzing transcriptional regulation of gene expressions. These methods build models that can explain a gene's expression level from the regulatory elements (features) on its promoter sequence. Different types of features, such as experimentally verified binding motifs, motifs discovered by computer programs, or transcription factor binding data measured with Chromatin Immunoprecipitation (ChIP) assays, have been used towards this goal. Each type of features has been shown successful in modeling gene transcriptional regulation under certain conditions. However, no comparison has been made to evaluate the relative merit of these features. Furthermore, most publicly available classification tools were not designed specifically for modeling transcriptional regulation, and do not allow the user to combine different types of features. RESULTS: In this study, we use a specific classification method, decision trees, to model transcriptional regulation in yeast with features based on predefined motifs, automatically identified motifs, ChlP-chip data, or their combinations. We compare the accuracies and stability of these models, and analyze their capabilities in identifying functionally related genes. Furthermore, we design and implement a user-friendly web server called CAGER (Classification Analysis of Gene Expression Regulation) that integrates several software components for automated analysis of transcriptional regulation using decision trees. Finally, we use CAGER to study the transcriptional regulation of Arabidopsis genes in response to abscisic acid, and report some interesting new results. CONCLUSION: Models built with ChlP-chip data suffer from low accuracies when the condition under which gene expressions are measured is significantly different from the condition under which the ChIP experiment is conducted. Models built with automatically identified motifs can sometimes discover new features, but their modeling accuracies may have been over-estimated in previous studies. Furthermore, models built with automatically identified motifs are not stable with respect to noises. A combination of ChlP-chip data and predefined motifs can substantially improve modeling accuracies, and is effective in identifying true regulons. The CAGER web server, which is freely available at http://cic.cs.wustl.edu/CAGER/, allows the user to select combinations of different feature types for building decision trees, and interact with the models graphically. We believe that it will be a useful tool to facilitate the discovery of gene transcriptional regulatory networks.
Algorithms↗
Growth hormone regulated gene expression.
Growth hormone (GH) regulated gene expression contributes to many of the effects of GH on cellular metabolism, growth and differentiation. Study of model systems has revealed several mechanisms by which GH regulates gene expression. Regulation of expression of the proto-oncogene c-fos involves STAT-, MAPK, and PI-3K-mediated changes in transcripton factors. STAT 5 plays important roles in regulation of spi 2.1 expression and in the sexually dimorphic expression of some liver genes. GH-regulated STAT 5 has also been implicated in regulation of other physiologically important genes, including those encoding components of the IGF-I axis and insulin. Together, these studies provide insight into GH signaling mechanisms and diverse physiological roles of GH.
Animals↗
A family of activator genes regulates expression of Rhizobium meliloti nodulation genes.
Nodulation (nod) gene expression in Rhizobium meliloti requires plant inducers and the activating protein product of the nodD gene. We have examined three genes in R. meliloti which have nodD activity and sequence homology. These three nodD genes are designated nodD1, nodD2 and nodD3, and have distinctive properties. The nodD1 gene product activates expression of the nodABC operon, as measured by a nodC-lacZ fusion or by transcript analysis, in the presence of crude seed or plant wash or the inducer, luteolin. The nodD3 gene product can cause a high basal (uninduced) level of nodC-lacZ expression and nodABC transcripts which is relatively unaffected by inducers. The effect of nodD3 is dependent on the presence of another gene, syrM (symbiotic regulator). By primer extension analysis we determined that the transcription start site is the same for nodD1 plus luteolin or nodD3-syrM mediated expression of nodA and nodH mRNAs. syrM also enhances the expression of another symbiotically important trait, production of extracellular polysaccharide. This regulatory effect of syrM requires locus syrA, which is linked to nodD3 and syrM. The syrM-syrA mediated increase in polysaccharide production requires at least some of the previously identified exo genes and may be a parallel regulatory event to the syrM-nodD3 control of nod promoters.
Blotting, Western↗
Transcription in four dimensions: nuclear receptor-directed initiation of gene expression.
Regulated gene expression, achieved through the coordinated assembly of transcription factors, co-regulators and the basal transcription machinery on promoters, is an initial step in accomplishing cell specificity and homeostasis. Traditional models of transcriptional regulation tend to be static, although gene expression profiles change with time to adapt to developmental and environmental cues. Furthermore, biochemical and structural studies have determined that initiation of transcription progresses through a series of ordered events. By integrating time into the analysis of transcription, chromatin immunoprecipitation assays and live-cell imaging techniques have revealed the dynamic, cooperative, functionally redundant and cyclical nature of gene expression. In this review, we present a dynamic model of gene transcription that integrates data obtained by these two techniques.
Animals↗
Cell cycle-regulated gene expression in Arabidopsis.
Regulated gene expression is an important mechanism for controlling cell cycle progression in yeast and mammals, and genes involved in cell division-related processes often show transcriptional regulation dependent on cell cycle position. Analysis of cell cycle processes in plants has been hampered by the lack of synchronizable cell suspensions for Arabidopsis, and few cell cycle-regulated genes are known. Using a recently described synchrony system, we have analyzed RNA from sequential samples of Arabidopsis cells progressing through the cell cycle using Affymetrix Genearrays. We identify nearly 500 genes that robustly display significant fluctuation in expression, representing the first genomic analysis of cell cycle-regulated gene expression in any plant. In addition to the limited number of genes previously identified as cell cycle-regulated in plants, we also find specific patterns of regulation for genes known or suspected to be involved in signal transduction, transcriptional regulation, and hormonal regulation, including key genes of cytokinin response. Genes identified represent pathways that are cell cycle-regulated in other organisms and those involved in plant-specific processes. The range and number of cell cycle-regulated genes show the close integration of the plant cell cycle into a variety of cellular control and response pathways.
Aphidicolin↗
Bovine papillomavirus E2 gene regulates expression of the viral E5 transforming gene.
We have performed transient-expression experiments with CV1 monkey kidney cells to investigate the role of the bovine papillomavirus type 1 (BPV1) E2 gene in the regulation of the E5 transforming gene. Direct analysis of the 7-kilodalton open reading frame (ORF) E5 protein and measurements of the expression of an E5-chloramphenicol acetyltransferase fusion protein indicate that the efficient expression of ORF E5 requires the full-length E2 gene, which can be supplied in trans. The viral long control region is required in cis for this response to ORF E2, and it acts in a position- and orientation-independent fashion characteristic of a transcriptional enhancer. Deletion analysis suggests that the P2443 promoter is required for efficient expression of the E5 gene. The E2 repressor activity encoded in the 3' end of the E2 gene inhibits the expression of ORF E5. These effects define a major BPV1 regulatory circuit and appear to explain the transformation behavior of a variety of BPV1 mutants.
Acetyltransferases↗
A potent far-upstream enhancer in the mouse pro alpha 2(I) collagen gene regulates expression of reporter genes in transgenic mice.
We have identified three DNase I-hypersensitive sites in chromatin between 15 and 17 kb upstream of the mouse pro alpha 2 (I) collagen gene. These sites were detected in cells that produce type I collagen but not in cells that do not express these genes. A construction containing the sequences from -17 kb to +54 bp of the mouse pro alpha 2 (I) collagen gene, cloned upstream of either the Escherichia coli beta-galactosidase or the firefly luciferase reporter gene, showed strong enhancer activity in transgenic mice when compared with the levels seen previously in animals harboring shorter promoter fragments. Especially high levels of expression of the reporter gene were seen in dermis, fascia, and the fibrous layers of many internal organs. High levels of expression could also be detected in some osteoblastic cells. When various fragments of the 5' flanking sequences were cloned upstream of the 350-bp proximal pro alpha 2(I) collagen promoter linked to the lacZ gene, the cis-acting elements responsible for enhancement were localized in the region between -13.5 and -19.5 kb, the same region that contains the three DNase I-hypersensitive sites. Moreover, the DNA segment from -13.5 to -19.5 kb was also able to drive the cell-specific expression of a 220-bp mouse pro alpha 1(I) collagen promoter, which is silent in transgenic mice. Hence, our data suggest that a far-upstream enhancer element plays a role in regulating high levels of expression of the mouse pro alpha 2(I) collagen gene.
3T3 Cells↗
Hypoxia regulates gene expression of alveolar epithelial transport proteins.
Alveolar hypoxia occurs during ascent to high altitude but is also commonly observed in many acute and chronic pulmonary disorders. The alveolar epithelium is directly exposed to decreases in O(2) tension, but a few studies have evaluated the effects of hypoxia on alveolar cell function. The alveolar epithelium consists of two cell types: large, flat, squamous alveolar type I and cuboidal type II (ATII). ATII cells are more numerous and have a number of critical functions, including transporting ions and substrates required for many physiological processes. ATII cells express 1) membrane proteins used for supplying substrates required for cell metabolism and 2) ion transport proteins such as Na(+) channels and Na(+)-K(+)-ATPase, which are involved in the vectorial transport of Na(+) from the alveolar to interstitial spaces and therefore drive the resorption of alveolar fluid. This brief review focuses on gene expression regulation of glucose transporters and Na(+) transport proteins by hypoxia in alveolar epithelial cells. Cells exposed to severe hypoxia (0% or 3% O(2)) for 24 h upregulate the activity and expression of the glucose transporter GLUT-1, resulting in preservation of ATP content. Hypoxia-induced increases in GLUT-1 mRNA levels are due to O(2) deprivation and inhibition of oxidative phosphorylation. This regulation occurs at the transcriptional level through activation of a hypoxia-inducible factor. In contrast, hypoxia downregulates expression and activity of Na(+) channels and Na(+)-K(+)-ATPase in cultured alveolar epithelial cells. Hypoxia induces time- and concentration-dependent decreases of alpha-, beta-, and gamma-subunits of epithelial Na(+) channel mRNA and beta(1)- and alpha(1)-subunits of Na(+)-K(+)-ATPase, effects that are completely reversed after reoxygenation. The mechanisms by which O(2) deprivation regulates gene expression of Na(+) transport proteins are not fully elucidated but likely involve the redox status of the cell. Thus hypoxia regulates gene expression of transport proteins in cultured alveolar epithelial type II cells differently, preserving ATP content.
Animals↗
Evidence for two control genes regulating expression of the quinic acid utilization (qut) gene cluster in Aspergillus nidulans.
The first three steps in quinic acid degradation in Aspergillus nidulans are catalysed by highly inducible enzymes encoded by a gene cluster regulated by an adjacent control region. Analysis of two non-inducible mutants has been done in diploid strains, where qutA8 is recessive and all three enzyme activities are fully induced in heterozygous qutA8/qutA+ diploids. In contrast, qutA4/qutA+ heterozygous diploids show semi-dominance of the mutant allele, giving markedly diminished growth on quinic acid and 30-40% decrease of enzyme induction. Strikingly, the qutA4/qutA8 heterozygous diploid grows to the same degree on quinic acid as the qutA4/qutA+ heterozygote and shows the same level of enzyme induction, whereas both the homozygous mutant diploids do not grow on quinic acid and show no enzyme induction. Therefore the two mutant genomes complement, identifying two distinct regulatory gene functions. A genetic model is proposed of a negatively acting gene (qutA) repressing expression of a positively acting gene (qutD, previously designated qutA8+) whose product is in turn required for expression of the three structural genes. The qutA4 mutation is interpreted to produce an altered repressor insensitive to quinic acid, and the qutD8 mutation the loss of activator protein. Close similarity in the regulation of the quinic acid gene cluster in Neurospora crassa suggests that the two types of control mutation, qalS and qalF, described for N. crassa may also reflect two regulatory genes.
Alcohol Oxidoreductases↗
Factors regulating lactoferrin gene expression.
Regulation of gene expression by nuclear receptors and transcription factors involves the concerted action of multiple proteins. The process of transcriptional activation involves chromatin modification, nuclear receptor or transcription factor binding to the response element of the promoter, and coregulator recruitment. Despite advances in knowledge pertaining to the molecular mechanisms of gene regulation overall, there is very limited information available on the molecular mechanism of lactoferrin gene regulation. This review will outline novel information relating to general gene regulation and will discuss the current understanding of the regulation of lactoferrin gene expression by nuclear receptors and transcription factors.
Animals↗
The neuroprotective WldS gene regulates expression of PTTG1 and erythroid differentiation regulator 1-like gene in mice and human cells.
Wallerian degeneration of injured neuronal axons and synapses is blocked in Wld(S) mutant mice by expression of an nicotinamide mononucleotide adenylyl transferase 1 (Nmnat-1)/truncated-Ube4b chimeric gene. The protein product of the Wld(S) gene localizes to neuronal nuclei. Here we show that Wld(S) protein expression selectively alters mRNA levels of other genes in Wld(S) mouse cerebellum in vivo and following transfection of human embryonic kidney (HEK293) cells in vitro. The largest changes, identified by microarray analysis and quantitative real-time polymerase chain reaction of cerebellar mRNA, were an approximate 10-fold down-regulation of pituitary tumour-transforming gene-1 (pttg1) and an approximate 5-fold up-regulation of a structural homologue of erythroid differentiation regulator-1 (edr1l-EST). Transfection of HEK293 cells with a Wld(S)-eGFP construct produced similar changes in mRNA levels for these and seven other genes, suggesting that regulation of gene expression by Wld(S) is conserved across different species, including humans. Similar modifications in mRNA levels were mimicked for some of the genes (including pttg1) by 1 mm nicotinamide adenine dinucleotide (NAD). However, expression levels of most other genes (including edr1l-EST) were insensitive to NAD. Pttg1(-/-) mutant mice showed no neuroprotective phenotype. Transfection of HEK293 cells with constructs comprising either full-length Nmnat-1 or the truncated Ube4b fragment (N70-Ube4b) demonstrated selective effects of Nmnat-1 (down-regulated pttg1) and N70-Ube4b (up-regulated edr1l-EST) on mRNA levels. Similar changes in pttg1 and edr1l-EST were observed in the mouse NSC34 motor neuron-like cell line following stable transfection with Wld(S). Together, the data suggest that the Wld(S) protein co-regulates expression of a consistent subset of genes in both mouse neurons and human cells. Targeting Wld(S)-induced gene expression may lead to novel therapies for neurodegeneration induced by trauma or by disease in humans.
Animals↗
Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDR-mediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1.
OBJECTIVE: The program of gene expression regulated by vascular endothelial growth factor (VEGF) remains poorly understood. The aim of this study was to identify VEGF-regulated genes in human umbilical vein endothelial cells. METHODS AND RESULTS: VEGF-regulated gene expression was analyzed by screening Affymetrix oligonucleotide arrays and quantitative, real-time, reverse transcription-polymerase chain reaction. The most strongly induced genes were the NR4A nuclear receptor family members Nur77, Nurr1, and Nor1 and the zinc-finger transcription factor Egr3. VEGF also induced rapid expression of Down syndrome candidate region 1, cyclooxygenase-2, tissue factor, stanniocalcin-1, the serine/threonine kinase Cot, and eps15 homology domain-containing protein. VEGF-induced NR4A family and Egr3 expression was blocked by a KDR inhibitor, and placental growth factor and basic fibroblast growth factor weakly increased expression of these genes. Induction of NR4A genes was mediated via intracellular Ca2+, protein kinase C- and calcineurin-dependent pathways. VEGF increased protein expression of Nurr1 and Nur77 and decreased Nur77 phosphorylation at the negative regulatory site serine 351. CONCLUSIONS: VEGF induces expression of NR4A nuclear receptors and Egr3 via KDR and KDR-mediated signaling mechanisms. The genes identified here are novel candidates as key early mediators of VEGF-induced endothelial functions.
Cells, Cultured↗
Glucose regulation of gene expression.
Regulation of gene expression by nutrients in mammals is an important mechanism allowing them to adapt to the nutritional environment. In-vivo and in-vitro experiments have demonstrated that the transcription of genes coding for lipogenic and glycolytic enzymes in liver and/or adipose tissue is upregulated by glucose. In order for glucose to act as a gene inducer, it must be metabolized. Recent evidence suggests that glucose-6-phosphate is the signal metabolite in the liver. DNA glucose response elements have been characterized and they have in common the presence of two sequences 5'-CACGTG-3' separated by five nucleotides, which bind in vitro a transcription factor of the basic domain, helix-loop-helix, leucine zipper family called USF/MLTF. Experiments concerning the potential role of USF/MLTF in the glucose response have led to opposite results, suggesting that USF/MLTF might not be the only factor involved. Finally, the glucose effect involves a kinase/phosphatase system. The kinase could be the AMP-activated protein kinase, the mammalian analogue of a yeast kinase, or SNF 1 which is important for the derepression of glucose-inhibited genes.
Animals↗
Gene expression regulated by gene VI of caulimovirus: transactivation of downstream genes of transcripts by gene VI of peanut chlorotic streak virus in transgenic tobacco.
Here we document that the gene VI product of peanut chlorotic streak virus (PClSV), a newly characterized member of the group, transactivates the translation of dicistronic transcripts. Dicistronic expression units have been analyzed both in protoplast transient expression experiments and in transgenic tobacco plants. Transgenic plants containing a dicistronic transcription unit (PClSV-gene VII-GUS) under the control of PClSV full-length transcript promoter with its long leader sequence show a relatively high abundance of the expected transcript but very little, or no, GUS activity. However, high GUS activity is found when gene VI protein is then provided by subsequent infection with PClSV. The efficient translation of polycistronic mRNAs mediated by gene VI of caulimovirus has potential value in product engineering of plants.
Base Sequence↗