Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The yeast transcriptional repressor Tup1, tethered to DNA, represses to strikingly different degrees transcription elicited by members of two classes of activators. Repression in both cases is virtually eliminated by mutation of either member of the cyclin-kinase pair Srb10/11. In contrast, telomeric chromatin affects both classes of activators equally, and in neither case is that repression affected by mutation of Srb10/11. In vitro, Tup1 interacts with RNA polymerase II holoenzyme bearing Srb10 as well as with the separated Srb10. These and other findings indicate that at least one aspect of Tup1's action involves interaction with the RNA polymerase II holoenzyme.
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PMID:Interaction of a transcriptional repressor with the RNA polymerase II holoenzyme plays a crucial role in repression. 1122 76

The Streptococcus pneumoniae mal regulon contains two operons, malXCD and malMP involved in the uptake and utilization of maltosaccharides. Both operons are transcribed from two divergent promoters, P(X) and P(M), and are negatively regulated by the MalR transcriptional repressor. Purified MalR protein binds to two DNA regions that encompasses both promoters, thus occupying its two operators, O(M) and O(X). However, the levels of occupation and repression were different, being higher when MalR was bound to O(M) than when it was anchored to O(X). Competition experiments between MalR and the Escherichia coli RNA polymerase on promoters P(M) and P(X) showed that the affinity of either protein for the promoter/operator DNA sequences was important to determine the frequency of transcription initiation. In addition to the control exerted by MalR, expression from promoter P(M) was affected by upstream sequences located within or close to P(X) promoter.
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PMID:MalR-mediated regulation of the Streptococcus pneumoniae malMP operon at promoter PM. Influence of a proximal divergent promoter region and competition between MalR and RNA polymerase proteins. 1127 84

High mobility protein-1 (HMG-1) has been shown to regulate transcription by RNA polymerase II. In the context that it acts as a transcriptional repressor, it binds to the TATA-binding protein (TBP) to form the HMG-1/TBP/TATA complex, which is proposed to inhibit the assembly of the preinitiation complex. By using electrophoretic mobility shift assays, we show that the acidic C-terminal domain of HMG-1 and the N terminus of human TBP are the domains that are essential for the formation of a stable HMG-1/TBP/TATA complex. HMG-1 binding increases the affinity of TBP for the TATA element by 20-fold, which is reflected in a significant stimulation of the rate of TBP binding, with little effect on the dissociation rate constant. In support of the binding target of HMG-1 being the N terminus of hTBP, the N-terminal polypeptide of human TBP competes with and inhibits HMG-1/TBP/TATA complex formation. Deletion of segments of the N terminus of human TBP was used to map the region(s) where HMG-1 binds. These findings indicate that interaction of HMG-1 with the Q-tract (amino acids 55-95) in hTBP is primarily responsible for stable complex formation. In addition, HMG-1 and the monoclonal antibody, 1C2, specific to the Q-tract, compete for the same site. Furthermore, calf thymus HMG-1 forms a stable complex with the TBP/TATA complex that contains TBP from either human or Drosophila but not yeast. This is again consistent with the importance of the Q-tract for this stable interaction and shows that the interaction extends over many species but does not include yeast TBP.
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PMID:The binding interaction of HMG-1 with the TATA-binding protein/TATA complex. 1139 Mar 76

In this work, we characterize genes in Mycobacterium tuberculosis that are regulated by IdeR (iron-dependent regulator), an iron-responsive DNA-binding protein of the DtxR family that has been shown to regulate iron acquisition in Mycobacterium smegmatis. To identify some of the genes that constitute the IdeR regulon, we searched the M. tuberculosis genome for promoter regions containing the consensus IdeR/DxR binding sequence. Genes preceded by IdeR boxes included a set encoding proteins necessary for iron acquisition, such as the biosynthesis of siderophores (mbtA, mbtB, mbtI), aromatic amino acids (pheA, hisE, hisB-like) and others annotated to be involved in the synthesis of iron-storage proteins (bfrA, bfrB). Some putative IdeR-regulated genes identified in this search encoded proteins predicted to be engaged in the biosynthesis of lipopolysaccharide (LPS)-like molecules (rv3402c), lipids (acpP) and peptidoglycan (murB). We analysed four promoter regions containing putative IdeR boxes, mbtA-mbtB, mbI, rv3402c and bfrA-bfd, for interaction with IdeR and for iron-dependent expression. Gel retardation experiments and DNase footprinting analyses with purified IdeR showed that IdeR binds to these IdeR boxes in vitro. Analysis of the promoters by primer extension indicated that the IdeR boxes are located near the -10 position of each promoter, suggesting that IdeR acts as a transcriptional repressor by blocking RNA polymerase binding. Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) coupled to molecular beacons, we showed that mRNA levels of mbtA, mbtB, mbtI, rv3402c and bfd are induced 14- to 49-fold in cultures of M. tuberculosis starved for iron, whereas mRNA levels of bfrA decreased about threefold. We present evidence that IdeR not only acts as a transcriptional repressor but also functions as an activator of bfrA. Three of the IdeR- and iron-repressed genes, mbtB, mbtI and rv3402c, were induced during M. tuberculosis infection of human THP-1 macrophages.
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PMID:The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. 1172 47

The death effector domain (DED) is a protein/protein interaction domain only found in proteins that are involved in apoptosis signaling. DEDD is a novel apoptosis signaling molecule that carries an N-terminal DED with complete sequence identity between the murine, rat, bovine and human domains. We previously identified two nuclear localization signals (NLS) responsible for DEDDs nuclear localization when transiently expressed. Using a new anti-DEDD antibody that allows us to stain endogenous DEDD in immunofluorescence microscopy we now detect a significant amount of DEDD in nucleoli of all cells tested. When overexpressed, DEDD localizes to nucleoli-like structures, activates caspase-6 and specifically inhibits RNA polymerase I (Pol I) dependent transcription in vivo as shown by blockage of BrUTP incorporation. The DED in DEDD is sufficient for its DNA binding, caspase-6 activating and Pol I specific transcriptional repressor activity. We have identified a third NLS in DEDD and only mutation of all three NLS generated a protein, DEDD Delta NLS1-3, that mainly localized to the cytoplasm. This protein no longer induced apoptosis, indicating that in contrast to other DED proteins, such as FADD, caspase-8 or c-FLIP, DEDD induces apoptosis from within the nucleus. This effect is abolished when specific point mutations are made within the DED. The DED in DEDD therefore represents a novel domain that is structurally similar to other DEDs but functionally different from classical DEDs found in FADD or caspase-8.
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PMID:Nuclear localization of DEDD leads to caspase-6 activation through its death effector domain and inhibition of RNA polymerase I dependent transcription. 1175 64

The basic helix-loop-helix (bHLH) transcription factor, Hand1, plays an important role in the development of the murine extra-embryonic trophoblast cell lineage. In the present study, we have analysed the expression of Hand1 in human extra-embryonic cell types and determined its binding specificity and transcriptional activity upon interaction with different class A bHLH factors. Northern blotting and in situ hybridization showed that Hand1 mRNA is specifically expressed in amnion cells at different stages of gestation. Accordingly, we demonstrate that the protein is exclusively produced in the amniotic epithelium in vivo and in purified amnion cells in vitro using a novel polyclonal Hand1 antiserum. Reverse transcriptase-PCR and immunohistochemical staining of blastocysts revealed the production of Hand1 mRNA and polypeptide in the trophectodermal cell layer. In the presence of E12/E47, Hand1 stimulated the transcription of luciferase reporters harbouring degenerate E-boxes, suggesting that E-proteins are potential dimerization partners in trophoblastic tumour and amnion cells. In contrast, Hand1 diminished E12/E47-dependent transcription of reporters containing perfect E-boxes by inhibiting the interaction of Hand1/E-protein heterodimers with the palindromic cognate sequence. Furthermore, we show that Hand1 down-regulated GAL-E12-dependent reporter expression, indicating that the protein can also act directly as a transcriptional repressor. Mutational analyses of GAL-Hand1 suggested that two protein regions located within its N-terminal portion mainly confer the repressing activity. In conclusion, human Hand1 may play an important role in the differentiation of the amniotic membrane and the pre-implanting trophoblast. Furthermore, the data suggest that Hand1 can act as a repressor by two independent mechanisms; sequestration of class A bHLH factors from E-boxes and inhibition of their transcriptional activity.
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PMID:Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains. 1180 95

Low temperature, drought, and high salinity induce the expression of many plant genes. To understand the mechanisms for the transcriptional activation of these genes, we conducted a reporter gene-aided genetic screen in Arabidopsis. Seven allelic mutations in the FIERY2 (FRY2) locus result in significant increases in the expression of stress-responsive genes with the DRE/CRT (drought-responsive/C-repeat) cis element but non-DRE/CRT type stress-responsive genes were less affected. The specific regulation of DRE/CRT class of genes by FRY2 appears to be caused by repression of stress induction of the upstream CBF/DREB transcription factor genes. fry2 mutants show increased tolerance to salt stress and to abscisic acid during seed germination but are more sensitive to freezing damage at the seedling stage. FRY2/CPL1 encodes a novel transcriptional repressor harboring two double-stranded RNA-binding domains and a region homologous to the catalytic domain of RNA polymerase II C-terminal domain phosphatases found in yeast and in animals that regulate gene transcription. These data indicate that FRY2 is an important negative regulator of stress gene transcription and suggest that structured RNA may regulate hormone and stress responses in plants as it does in animals.
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PMID:Repression of stress-responsive genes by FIERY2, a novel transcriptional regulator in Arabidopsis. 1214 53

Recruitment of TATA-binding protein (TBP) is central to activation of transcription by RNA polymerase II (pol II). This depends upon co-activator proteins including TBP-associated factors (TAFs). Yeast Mot1p was identified as a general transcriptional repressor in genetic screens and is also found associated with TBP. To obtain insight into Mot1p function in vivo, we determined the mRNA expression profile of the mot1-1 temperature-sensitive (Ts) strain. Unexpectedly, this indicated that Mot1p mostly plays a positive role for transcription. For one potential activation target, HXT2, we analyzed promoter recruitment of Mot1p, TBP, Taf1p (Taf130p) and pol II by chromatin immunoprecipitation assays. Whereas TBP becomes stably associated upon activation of the HXT2 and HXT4 promoters, Mot1p showed only a transient association. TBP recruitment was compromised in two different mot1 mutant strains, but was only moderately affected in a taf1 Ts strain. Together, our data indicate that Mot1p can assist in recruitment of TBP on promoters during gene activation in vivo.
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PMID:Mot1p is essential for TBP recruitment to selected promoters during in vivo gene activation. 1235 33

The positive transcription elongation factor b (P-TEFb) contains cyclin T1 (CycT1) and cyclin-dependent kinase 9 (Cdk9). For activating the expression of eukaryotic genes, the histidine-rich sequence in CycT1 binds the heptapeptide repeats in the C-terminal domain (CTD) of RNA polymerase II (RNAPII), whereupon Cdk9 phosphorylates the CTD. We found that alanine-substituted heptapeptide repeats that cannot be phosphorylated also bind CycT1. When placed near transcription units, these CTD analogs block effects of P-TEFb. Remarkably, the transcriptional repressor PIE-1 from Caenorhabditis elegans behaves analogously. It binds CycT1 via an alanine-containing heptapeptide repeat and inhibits transcriptional elongation. Thus, our findings reveal a new mechanism by which repressors inhibit eukaryotic transcription.
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PMID:A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFb. 1265 93

Celiac disease (CD) is an enteropathy characterized by a Th1-type immune response to the dietary gluten. The transcriptional mechanisms or factors that control Th1 cell development in this condition remain to be elucidated. The aim of this study was to analyze in CD the expression of interferon (IFN) regulatory factor (IRF)-1, a transcription factor that regulates the differentiation and function of Th1 cells. Duodenal biopsies were taken from children with untreated CD and control children, and analyzed for IRF-1 by Southern blotting of reverse-transcriptase PCR products and Western blotting. IRF-1 DNA-binding activity was assessed by electrophoretic shift mobility assay. The effect of gliadin stimulation on IRF-1 induction was investigated in an ex vivo organ culture of treated CD biopsies. Enhanced IRF-1 was seen in untreated CD in comparison with controls. This was evident at both the RNA and protein level. Furthermore, untreated CD samples exhibited stronger nuclear accumulation and DNA-binding activity of IRF-1 than controls. In contrast, IRF-2, a transcriptional repressor that binds the same DNA element and competes with IRF-1, was expressed at the same level in nuclear proteins extracted from both untreated CD and control patients. In explant cultures of treated CD biopsies, gliadin enhanced both IRF-1 RNA and protein. This effect was prevented by a neutralizing IFN-gamma antibody. Furthermore, stimulation of normal duodenal biopsies with IFN-gamma enhanced IRF-1. These data indicate that IRF-1 is a hallmark of the gliadin-mediated inflammation in CD and suggest that IFN-gamma/IRF-1 signaling pathway can play a key role in maintaining and expanding the local Th1 inflammatory response in this disease.
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PMID:Enhanced expression of interferon regulatory factor-1 in the mucosa of children with celiac disease. 1278 88


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