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At least 883 records · Page 49Linked to original sources
PubMed2005

SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions.

SIP1/ZEB2 is a member of the deltaEF-1 family of two-handed zinc finger nuclear factors. The expression of these transcription factors is associated with epithelial mesenchymal transitions (EMT) during development. SIP1 is also expressed in some breast cancer cell lines and was detected in intestinal gastric carcinomas, where its expression is inversely correlated with that of E-cadherin. Here, we show that expression of SIP1 in human epithelial cells results in a clear morphological change from an epithelial to a mesenchymal phenotype. Induction of this epithelial dedifferentiation was accompanied by repression of several cell junctional proteins, with concomitant repression of their mRNA levels. Besides E-cadherin, other genes coding for crucial proteins of tight junctions, desmosomes and gap junctions were found to be transcriptionally regulated by the transcriptional repressor SIP1. Moreover, study of the promoter regions of selected genes by luciferase reporter assays and chromatin immunoprecipitation shows that repression is directly mediated by SIP1. These data indicate that, during epithelial dedifferentiation, SIP1 represses in a coordinated manner the transcription of genes coding for junctional proteins contributing to the dedifferentiated state; this repression occurs by a general mechanism mediated by Smad Interacting Protein 1 (SIP1)-binding sites.

Binding Sites↗
PubMed1994

Repression of retinoic acid-induced transactivation by embryonal LTR binding protein.

The mechanism of repression of transcription by ELP, the embryonal long terminal repeat binding protein, was investigated. ELP represses the Moloney murine leukemia virus long terminal repeat by binding to a site which overlaps with a sequence element for retinoic acid receptor binding. This suggests possible competition of ELP with retinoic acid receptor for the same sequence elements. Oligonucleotides corresponding to ELP and/or retinoic acid receptor binding elements were placed upstream of the SV40 promoter and their effect on gene expression was analyzed by CAT assay. Elements which have affinity to both ELP and retinoic acid receptor were activated by retinoic acid receptor and these activations were repressed by ELP. An ELP binding element without affinity to retinoic acid receptor was insensitive to both activation by retinoic acid receptor and repression by ELP. Furthermore, cellular ELP binding elements and the Moloney leukemia virus long terminal repeat were activated by retinoic acid. These data suggest that one of the mechanism of transcriptional repression by ELP is competition for binding sites with transactivators such as retinoic acid receptors.

3T3 Cells↗
PubMed2003

An auxin-repressed gene (RpARP) from black locust (Robinia pseudoacacia) is posttranscriptionally regulated and negatively associated with shoot elongation.

The plant hormone auxin regulates various growth and developmental processes by controlling the expression of auxin-response genes. While many genes up-regulated by auxin have been characterized, less is known about the genes that are down-regulated by auxin. We isolated and characterized an auxin-repressed gene (RpARP) from the tree legume, Robinia pseudoacacia L. A sequence similarity search in public databases showed that the RpARP gene has homologs in various higher plants including monocots and dicots. The deduced amino acid sequences are highly conserved among these homologs (up to 85% identity). Northern blot analysis showed that auxin repressed RpARP gene expression and that repression was dependent on the presence of metabolizable sugar and on protein synthesis. In addition, cold treatment abolished the auxin-mediated repression of RpARP gene expression. Results from transgenic plant analyses suggest that RpARP gene expression is posttranscriptionally regulated by auxin and by the untranslated regions. Sequence analysis of the promoter region (-70 and -500 bp upstream of the putative transcription initiation site) of the RpARP gene identified four sucrose-repressible response elements (TATCCAT-motifs; Huang et al. 1990), suggesting that the cis-elements responsible for regulation by sucrose are located in the promoter region. In fact, the expression of the transgenic RpARP gene was unaffected by sucrose when driven by a CaMV 35S promoter. We present evidence that RpARP gene expression is negatively associated with hypocotyl elongation.

Arabidopsis↗
PubMed2001

Regulation of zygotic gene activation in the preimplantation mouse embryo: global activation and repression of gene expression.

Superimposed on the activation of the embryonic genome in the preimplantation mouse embryo is the formation of a transcriptionally repressive state during the two-cell stage. This repression appears mediated at the level of chromatin structure, because it is reversed by inducing histone hyperacetylation or inhibiting the second round of DNA replication. We report that of more than 200 amplicons analyzed by mRNA differential display, about 45% of them are repressed between the two-cell and four-cell stages. This repression is scored as either a decrease in amplicon expression that occurs between the two-cell and four-cell stages or on the ability of either trichostatin A (an inhibitor of histone deacetylases) or aphidicolin (an inhibitor of replicative DNA polymerases) to increase the level of amplicon expression. Results of this study also indicate that about 16% of the amplicons analyzed likely are novel genes whose sequence doesn't correspond to sequences in the current databases, whereas about 20% of the sequences expressed during this transition likely are repetitive sequences. Lastly, inducing histone hyperacetylation in the two-cell embryos inhibits cleavage to the four-cell stage. These results suggest that genome activation is global and relatively promiscuous and that a function of the transcriptionally repressive state is to dictate the appropriate profile of gene expression that is compatible with further development.

Acetylation↗
PubMed1998

Transcriptional repression by the Epstein-Barr virus EBNA3A protein tethered to DNA does not require RBP-Jkappa.

The Epstein-Barr virus (EBV) proteins EBNA1, EBNA2, EBNA3A, EBNA3C, LMP1 and EBNA-LP are essential for the in vitro immortalization of primary B lymphocytes by EBV. EBNA2 is a transcriptional activator of viral and cellular genes. Both EBNA3A and EBNA3C have been shown to specifically inhibit EBNA2-activated transcription by direct interaction with RBP-Jkappa, a cellular DNA-binding factor known to recruit EBNA2 to EBNA2-responsive genes. This interaction interferes with the binding of RBP-Jkappa to DNA in vitro, and this is probably the mechanism by which EBNA3A and EBNA3C repress EBNA2-activated transcription in vivo. EBNA3A and EBNA3C also directly repress transcription when tethered to a promoter via the DNA-binding domain of the yeast Gal4 protein. As RBP-Jkappa has been previously shown to be a repressor in mammalian cells, this repression could be due to the recruitment of RBP-Jkappa by Gal4-EBNA3A and 3C. In this study, we have precisely mapped the domain of EBNA3A involved in the interaction with RBP-Jkappa and we have shown that interaction with RBP-Jkappa is not required for the Gal4-EBNA3A-mediated repression. Furthermore, we have characterized in EBNA3A a domain of 143 amino acids which is necessary and sufficient for EBNA3A-dependent repression.

DNA-Binding Proteins↗
PubMed1991

Catabolite repression by galactose in overexpressed GAL4 strains of Saccharomyces cerevisiae.

Catabolite repression by galactose was investigated in several strains of Saccharomyces cerevisiae grown on different carbon sources. Galactose repressed as much as glucose; raffinose was less effective. Full derepression was achieved with lactate. The functions tested were L-lactate ferricytochrome c oxidoreductase, NAD-glutamate dehydrogenase, and respiration. Galactose repression was observed only in the GAL4 but not in the gal4 strain. The presence of multiple copies of the GAL4 gene enhanced the repression by galactose. Different alleles of the GAL4 gene and the copy number did not affect glucose repression.

Alleles↗
PubMed1997

FNR-dependent repression of ndh gene expression requires two upstream FNR-binding sites.

The ndh gene of Escherichia coli encodes a non-proton-translocating NADH dehydrogenase (NdhII) that is anaerobically repressed by the global transcription regulator, FNR. FNR binds at two sites (centred at -50.5 and -94.5) in the ndh promoter but the mechanism of FNR-mediated repression appears not to be due to promoter occlusion. This mechanism has been investigated using an aerobically active derivative of FNR, FNR* (FNR-D154A), with ndh promoters containing altered FNR-binding sites. FNR* repressed ndh gene expression both aerobically and anaerobically in vivo. Gel retardation analysis and DNase I footprinting with purified FNR* protein confirmed that FNR interacts at two sites in the ndh promoter, and that FNR and RNA polymerase (RNAP) can bind simultaneously. Studies with three altered ndh promoters, each containing an impaired or improved FNR-site, indicated that both FNR-sites are needed for efficient repression in vivo. The alpha-subunit of RNAP interacted with two regions (centred at -105 and -46), each overlapping one of the FNR-sites in the ndh promoter. Footprints of the FNR*-RNAP-ndh ternary complex indicated that FNR*-binding at -50.5 prevents the alpha-subunit of RNAP from docking with the DNA just upstream of the -35 element. Binding of a second FNR* molecule at the -105 site likewise prevents binding of the alpha-subunit at its alternative site, thus providing a plausible mechanism for FNR-mediated repression based on displacement of the alpha-subunit of RNAP.

Aerobiosis↗
PubMed2000

Catabolite repression of dra-nupC-pdp operon expression in Bacillus subtilis.

Expression of the Bacillus subtilis dra-nupC-pdp operon is subject to catabolite repression by glucose. It was shown that a cis-acting catabolite-responsive element (CRE) sequence located 64 bp downstream of the transcription-start site mediated catabolite repression of the dra-nupC-pdp operon as it does for many other B. subtilis genes. Point mutations in the CRE sequence caused the loss of catabolite repression of the operon. Catabolite repression of dra-nupC-pdp expression was relieved in a ccpA mutant and was found to be dependent on both HPr and the HPr-like protein Crh. Furthermore, a transcription-repair coupling factor, Mfd, was also found to be involved in the glucose repression of dra-nupC-pdp expression. By the use of in vitro gel mobility shift analysis, a specific HPr-P dependent binding of CcpA to the dra CRE site was demonstrated.

Bacillus subtilis↗
PubMed2002

Effect of vfr mutation on global gene expression and catabolite repression control of Pseudomonas aeruginosa.

Vfr of Pseudomonas aeruginosa is 91% similar to the cAMP receptor protein (CRP) of Escherichia coli. Based on the high degree of sequence homology between the two proteins, the question arose whether Vfr had a global regulatory effect on gene expression for P. aeruginosa as CRP did for E. coli. This report provides two-dimensional polyacrylamide gel electrophoretic evidence that Vfr is a global regulator of gene expression in P. aeruginosa. In a vfr101::aacC1 null mutant, at least 43 protein spots were absent or decreased when compared to the proteome pattern of the parent strain. In contrast, 17 protein spots were absent or decreased in the parent strain when compared to the vfr101::aacC1 mutant. Thus, a mutation in vfr affected production of at least 60 proteins in P. aeruginosa. In addition, the question whether Vfr and CRP shared similar mechanistic characteristics was addressed. To ascertain whether Vfr, like CRP, can bind cAMP, Vfr and CRP were purified to homogeneity and their apparent dissociation constants (K(d)) for binding to cAMP were determined. The K(d) values were 1.6 microM for Vfr and 0.4 microM for CRP, suggesting that these proteins have a similar affinity for cAMP. Previously the authors had demonstrated that Vfr could complement a crp mutation and modulate catabolite repression in E. coli. This study presents evidence that Vfr binds to the E. coli lac promoter and that this binding requires the presence of cAMP. Finally, the possible involvement of Vfr in catabolite repression control in P. aeruginosa was investigated. It was found that succinate repressed production of mannitol dehydrogenase, glucose-6-phosphate dehydrogenase, amidase and urocanase both in the parent and in two vfr null mutants. This implied that catabolite repression control was not affected by the vfr null mutation. In support of this, the cloned vfr gene failed to complement a mutation in the P. aeruginosa crc gene. Thus, although Vfr is structurally similar to CRP, and is a global regulator of gene expression in P. aeruginosa, Vfr is not required for catabolite repression control in this bacterium.

Bacterial Proteins↗
PubMed1994

Regulation of transfer genes of promiscuous IncP alpha plasmid RK2: repression of Tra1 region transcription both by relaxosome proteins and by the Tra2 regulator TrbA.

The Tra1 region of broad host range IncP alpha plasmid RK2 encodes proteins essential for its promiscuous conjugative transfer and includes oriT, the site at which nicking occurs to initiate transfer replication. Unregulated expression of the Tra1 region genes would be likely to place a major burden on the host. To investigate the control of these genes the three transcriptional promoters from this region were cloned by PCR and inserted into xylE promoter probe vectors. The strength of traJp and traKp was estimated to be six to eightfold less than the strong trfA promoter which is required for expression of genes for vegetative replication of RK2. The traG promoter was about one-tenth the strength of the other two. These promoters are not repressed by products of the central control operon of RK2. However, traJp and traKp, which are arranged as back to back divergent promoters in the oriT region, are repressed by TraK which constitutes part of the relaxosome necessary for nicking at oriT. A second relaxosome protein, TraJ, represses traJp. traGp is not repressed by any relaxosome proteins. All three promoters are repressed by TrbA, which is encoded at the start of the trb operon containing the rest of the transfer genes (the Tra2 region). These circuits provide: (i) an autoregulatory way of ensuring production of enough relaxosome proteins without overburdening the host; and (ii) a means of coordinating expression of both blocks of transfer genes.

Bacterial Outer Membrane Proteins↗
PubMed1999

Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a.

There is growing evidence that the p53 tumor suppressor protein not only can function to activate gene transcription but also to repress the expression of specific genes. Although recent studies have implicated the transcriptional repression function of p53 in the pathway of apoptosis, the molecular basis of this activity remains poorly understood. This study takes a first step toward elucidating this mechanism. We report that trichostatin A (TSA), an inhibitor of histone deacetylases (HDACs), abrogates the ability of p53 to repress the transcription of two genes that it negatively regulates, Map4 and stathmin. Consistent with this finding, we report that p53 physically associates in vivo with HDACs. This interaction is not direct but, rather, is mediated by the corepressor mSin3a. Both wild-type p53 and mSin3a, but not mutant p53, can be found bound to the Map4 promoter at times when this promoter preferentially associates with deacetylated histones in vivo. Significantly, inhibition of p53-mediated transcriptional repression with TSA markedly inhibits apoptosis induction by p53. These data offer the first mechanistic insights for p53-mediated transcriptional repression and underscore the importance of this activity for apoptosis induction by this protein.

Animals↗
PubMed1999

Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor.

The N-CoR/SMRT complex containing mSin3 and histone deacetylase (HDAC) mediates transcriptional repression by nuclear hormone receptors and Mad. The proteins encoded by the ski proto-oncogene family directly bind to N-CoR/SMRT and mSin3A, and forms a complex with HDAC. c-Ski and its related gene product Sno are required for transcriptional repression by Mad and thyroid hormone receptor (TRbeta). The oncogenic form, v-Ski, which lacks the mSin3A-binding domain, acts in a dominant-negative fashion, and abrogates transcriptional repression by Mad and TRbeta. In ski-deficient mouse embryos, the ornithine decarboxylase gene, whose expression is normally repressed by Mad-Max, is expressed ectopically. These results show that Ski is a component of the HDAC complex and that Ski is required for the transcriptional repression mediated by this complex. The involvement of c-Ski in the HDAC complex indicates that the function of the HDAC complex is important for oncogenesis.

Animals↗
PubMed2005

DNA looping-mediated repression by histone-like protein H-NS: specific requirement of Esigma70 as a cofactor for looping.

Transcription initiation by RNA polymerase (RNP) carrying the house-keeping sigma subunit, sigma70 (Esigma70), is repressed by H-NS at a number of promoters including hdeABp in Escherichia coli, while initiation with RNP carrying the stationary phase sigma, sigma38 (Esigma38), is not. We investigated the molecular mechanism of selective repression by H-NS to identify the differences in transcription initiation by the two forms of RNPs, which show indistinguishable promoter selectivities in vitro. Using hdeABp as a model promoter, we observed with purified components that H-NS, acting at a sequence centered at -118, selectively repressed transcription by Esigma70. This selective repression is attributed to the differences in the interactions between hdeABp and the two forms of RNPs, since no other factor is required for the repression. We observed that the two forms of RNPs could form an open initiation complex (RP(O)) at hdeABp, but that Esigma70 failed to initiate transcription in the presence of H-NS. Interestingly, KMnO4 assays and high-resolution atomic force microscopy (AFM) revealed that hdeABp DNA wrapped around Esigma70 more tightly than around Esigma38, resulting in the potential crossing over of the DNA arms that project out of Esigma70 . RP(O) but not out of Esigma38 . RP(O). Based on these observations, we postulated that H-NS bound at -118 laterally extends by the cooperative recruitment of H-NS molecules to the promoter-downstream sequence joined by wrapping of the DNA around Esigma70 . RP(O), resulting in effective sealing of the DNA loop and trapping of Esigma70. Such a ternary complex of H-NS . Esigma70 hdeABp was demonstrated by AFM. In this case, therefore, Esigma70 acts as a cofactor for DNA looping. Expression of this class of genes by Esigma38 in the stationary phase is not due to its promoter specificity but to the architecture of the promoter . Esigma38 complex.

Bacterial Proteins↗
PubMed1989

Position and density effects on repression by stationary and mobile DNA-binding proteins.

We have investigated the effects of two types of DNA-binding proteins on bacterial repression. First, the effects of operator positioning on repression by stationary DNA-binding proteins, the Lac repressor and the Trp repressor, were examined in vivo. Both operator number and positioning play a role in determining in vivo levels of repression. Operators located within a promoter are more efficient regulators than those positioned at the start of transcription. Second, we investigated the effects of DNA-binding protein density on repression using a mobile DNA-binding protein, Escherichia coli RNA polymerase. We employed a transcriptional interference assay using convergent transcriptional units. The strong synthetic promoter conI and its derivatives were observed to interfere with expression of the aadA gene, which confers spectinomycin resistance upon its host. Transcriptional interference by RNA polymerase occurred only in cis and had a strong dependence on polymerase density that was modulated by varying the promoter strengths. A change in the density of approximately fourfold completely abolished the observed transcriptional interference. Several models are discussed to explain the repression patterns observed for stationary and mobile DNA-binding proteins.

Base Sequence↗
PubMed2006

The transcription factor FLC confers a flowering response to vernalization by repressing meristem competence and systemic signaling in Arabidopsis.

Floral development at the Arabidopsis shoot apical meristem occurs in response to environmental cues that are perceived in different tissues. Photoperiod is detected in the vascular tissue of the leaf (phloem) and promotes production of a systemic signal that induces flowering at the meristem. Vernalization, the response to winter temperatures, overcomes a block on photoperiodic floral induction. In Arabidopsis, this block is caused by inhibitors of flowering that comprise several related MADS-box transcription factors, the most prominent of which is FLC. We show that FLC delays flowering by repressing production in the leaf of at least two systemic signals, one of which is controlled by the RAF kinase inhibitor-like protein FT. Reducing expression of these signals indirectly represses expression of genes involved in floral induction at the meristem. In addition, FLC expression in the meristem impairs response to the FT signal by directly repressing expression of the SOC1 MADS-box transcription factor and preventing up-regulation of the bZIP transcription factor FD. Repression of genes acting at multiple levels in this hierarchy is required for the extreme delay in flowering caused by FLC. An FLC:HA fusion protein binds directly in vivo to the promoter regions of FD and SOC1 and to the first intron of FT. Thus vernalization relieves transcriptional repression of key regulatory genes in both the leaf and meristem, allowing production of systemic signals in the leaves and conferring competence on the meristem to respond to these signals.

Arabidopsis↗
PubMed1991

Transcriptional regulation of a yeast HSP70 gene by heat shock factor and an upstream repression site-binding factor.

SSA1, one of the heat-inducible HSP70 genes in the yeast Saccharomyces cerevisiae, displays a significant basal level of expression under optimal growth conditions. Although multiple sites related to the heat shock element (HSE) consensus sequences are present in the SSA1 promoter region, one of these, HSE2, plays a key role in basal expression. An upstream repression site (URS) located adjacent to HSE2 causes repression of basal expression but has little effect on heat-inducible expression of SSA1. A series of DNase I footprinting assays suggests that heat shock factor (HSF) and a URS-binding factor (URSF) can bind simultaneously to the adjacent binding sites HSE2 and URS under optimal growth conditions. URSF in extracts from heat-shocked cells does not bind (or binds very poorly) to the URS adjacent to HSE2. However, URSF in these extracts is able to bind the URS if the URS is separated from HSE2 or if the HSE is mutated such that HSF binding is abolished. These in vitro experiments are consistent with in vivo results showing that the URS is able to repress transcription driven by HSE2 both before and after heat shock if it is separated from HSE2. Our results are consistent with a model of repression in which URSF and HSF bind simultaneously to the adjacent binding sites URS and HSE2 prior to heat shock. After heat shock, however, binding of the two proteins to the adjacent sites is exclusive, perhaps due to modification of HSF known to occur upon heat shock. Because HSF binding predominates, repression by URSF is relieved upon heat shock.

Base Sequence↗
PubMed1993

Replication-coupled chromatin assembly is required for the repression of basal transcription in vivo.

The chromatin assembly process coupled to DNA synthesis in the Xenopus oocyte nucleus is significantly more repressive toward basal transcription than chromatin assembly on duplex DNA. We show that chromatin assembly concurrent with DNA synthesis over the promoter region itself is causal for repression. However, the trans-activator Gal4-VP16 both relieves repression and activates transcription regardless of the chromatin assembly pathway. This activation is independent of whether Gal4-VP16 addition occurs before or after chromatin assembly. We propose that replication-coupled chromatin assembly represents a general mechanism to direct the efficient repression of basal transcription. However transcription induction by a specific activator, Gal4-VP16, occurs independent of this chromatin-mediated repression.

Animals↗
PubMed1994

Structure-function analysis of the TBP-binding protein Dr1 reveals a mechanism for repression of class II gene transcription.

Dr1, a repressor of class II genes, regulates transcription by a novel mechanism. Biochemical analyses reveal that Dr1 directly interacts with the multiprotein TFIID complex. By use of the yeast two-hybrid system, we demonstrate that the association of Dr1 with the TATA-binding protein (TBP) subunit of TFIID occurs in vivo. In addition, Dr1 can repress transcription from TATA-containing as well as TATA-less promoters in transient transfection assays. Importantly, Dr1-mediated repression can be reversed by overexpression of TBP in vivo. By use of diverse approaches, we mapped two distinct domains in Dr1 required for repression. One domain is essential for the Dr1-TBP interaction, and the second is rich in alanine residues. The TBP-binding domain of Dr1 cannot be replaced by a heterologous DNA-binding domain in mediating repression. We demonstrate that some, but not all, transcriptional activators can reverse Dr1-mediated repression in vivo.

Amino Acid Sequence↗