Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00001 (DNase I)
 8,324 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mb-1 gene, which encodes a protein associated with membrane-bound antibody, is expressed only at the early stages of B cell differentiation. To gain insight into the mechanisms that underlie temporally regulated gene expression, we examined the mb-1 promoter region for interactions with cell type-specific DNA binding proteins. Here, we report the characterization of a novel nuclear factor that recognizes the mb-1 promoter. This DNA binding activity, termed Early B cell Factor, or EBF, is expressed in early stage B cells, but not in late stage B cells, T cells or non-lymphoid cells. EBF recognizes the nucleotide sequence 5'-CAAGGGAAT-3' in the mb-1 and major histocompatibility complex (MHC) class II A alpha d promoters. The binding of EBF to DNA was characterized by DNase I footprinting and by methylation interference analysis which indicated both major and minor groove contacts. The specificity of EBF binding is distinct from that of other nuclear factors expressed in hematopoietic cells. EBF appears to consist of at least two polypeptides of approximately 70-75 kDa and 80-85 kDa. The EBF binding site was important for maximal mb-1 promoter activity in early stage B cells. Moreover, the EBF binding site conferred correct lineage- and stage-specific transcriptional activity upon a heterologous promoter in a context-dependent manner. Thus, EBF appears to represent an important transcriptional regulator of B cell specific gene expression.
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PMID:A novel lineage-specific nuclear factor regulates mb-1 gene transcription at the early stages of B cell differentiation. 191

Expression of the Saccharomyces cerevisiae gene encoding cytochrome b2 (EC 1.2.2.3), CYB2, was investigated by direct analysis of mRNA transcripts and by measurement of the expression of lacZ fused to the CYB2 control regions. These studies indicated that regulation of the CYB2 gene is subject to several metabolic controls at the transcriptional level: inhibition due to glucose fermentation, induction by lactate, and inhibition in anaerobiosis or in absence of heme biosynthesis. Furthermore, we have shown that the CYB2 promoter contains one cis negative regulatory region and two heme-dependent positive regions, one of which is controlled by the transcriptional regulator CYP1 (HAP1) which is involved in the modulation of the expression of several oxygen-regulated genes. The CYP1 (HAP1)-binding sequence was located by gel retardation and DNase I footprinting experiments and compared with the binding sequences previously characterized in detail (UAS1CYC1, UAS'CYP3 (CYC7), and UASCTT1).
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PMID:Complex transcriptional regulation of the Saccharomyces cerevisiae CYB2 gene encoding cytochrome b2: CYP1(HAP1) activator binds to the CYB2 upstream activation site UAS1-B2. 204 77

Genomic clones containing the 5'-terminal portion of the human CRE-BP1 gene that encodes transcriptional regulator binding to the cyclic AMP response element (CRE) were isolated. Multiple transcriptional start sites in the promoter region were identified by nuclease S1 mapping and primer extension analysis. By DNase I footprinting with use of purified transcription factor Sp1 and nuclear extracts prepared from HeLa cells, 11 Sp1-binding sites, two CCAAT sequences, two CREs, and three unknown factor recognition elements were found. Transfection of chimeric chloramphenicol acetyltransferase plasmids containing various deletions of the promoter into CV-1 cells indicated that the region between nucleotides -50 and 90, which contained three Sp1-binding sites and one CRE, was sufficient for basal promoter activity. These results suggest that multiple sequence-specific DNA-binding proteins may control the expression of the CRE-BP1 gene, although Sp1 seems to be important for the basal promoter activity.
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PMID:Promoter region of the human CRE-BP1 gene encoding the transcriptional regulator binding to the cyclic AMP response element. 214 72

The DNA-binding AbrB protein of Bacillus subtilis is an ambiactive transcriptional regulator of genes expressed during the transition state between vegetative growth and the onset of stationary phase and sporulation. Studies on the transcriptional control of AbrB synthesis using abrB-lacZ fusions indicated that the abrB gene was autoregulated. This was consistent with the observation that purified AbrB protein bound specifically to the promoter region of its own gene in DNase I protection experiments. The structural gene mutation abrB4 abolished the autoregulation and purified AbrB4 protein did not have the promoter binding properties associated with the wild-type protein. Both AbrB and AbrB4 proteins were shown to be hexamers of 10,500 Dalton subunits and subunit exchange occurred between the proteins in vitro. However, the presence of only one or two mutant subunits dramaticaly altered the DNA-binding ability of the multimeric protein. The results support a model in which autoregulation of the abrB gene is an important factor in preventing sporulation-associated genes from being expressed during vegetative growth.
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PMID:The transition state transcription regulator AbrB of Bacillus subtilis is autoregulated during vegetative growth. 250 67

Zif268, a zinc finger protein whose mRNA is rapidly activated in cells exposed to growth factors or other signaling agents, is thought to play a role in regulating the genetic program induced by extracellular ligands. We report that Zif268 has one of the characteristics of a transcriptional regulator, namely, sequence-specific binding to DNA. Zif268 synthesized in Escherichia coli bound to two sites upstream of the zif268 gene and to sites in the promoter regions of other genes. The nucleotide sequences responsible for binding were defined by DNase I footprinting, by methylation interference experiments, and by use of synthetic oligonucleotides. From these results we derived the following consensus sequence for a Zif268 high-affinity binding site: GCGTGGGGCG.
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PMID:DNA binding site of the growth factor-inducible protein Zif268. 251 Jan 70

The virC and virD operons of the virulence region of the Ti plasmid are highly regulated, requiring a transcriptional regulator that is encoded by virG and is activated by the product of virA and plant phenolics such as acetosyringone. Full expression of virC and virD of octopine and nopaline Ti plasmids is also obtained by a mutation in the ros gene of the Agrobacterium tumefaciens chromosome. S1-nuclease analysis, in vitro transcription, and DNase I protection experiments with A. tumefaciens RNA polymerase revealed virD promoters tandemly arranged, both of which are functional in the Ros mutant, while only one is functional in the presence of acetosyringone. A third (overlapping) promoter appears to be responsible for transcription of virC. Expression of virC and virD appears to be modulated by factors within the bacterium by means of a mechanism that is independent of factors produced during infection of the host plant.
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PMID:Regulation of the virC and virD promoters of pTiC58 by the ros chromosomal mutation of Agrobacterium tumefaciens. 284 May 54

Simultaneous resistance to an array of drugs with different cytotoxic activities is a property of Saccharomyces cerevisiae, in which the protein Pdr3p has recently been shown to play a role as a transcriptional regulator. We provide evidence that the yeast PDR3 gene, which encodes a zinc finger transcription factor implicated in certain drug resistance phenomena, is under positive autoregulation by Pdr3p. DNase I footprinting analyses using bacterially expressed Pdr3p showed specific recognition by this protein of at least two upstream activating sequences in the PDR3 promoter. The use of lacZ reporter constructs, a mutational analysis of the upstream activating sequences, as well as band shift experiments enabled the identification of two 5'TC CGCGGA3' sequence motifs in the PDR3 gene as consensus elements for the binding of Pdr3p. Several similar sequence motifs can be found in the promoter of PDR5, a gene encoding an ATP-dependent drug pump whose Pdr3p-induced overexpression is responsible for drug resistance phenomena. Recently one of these sequence elements was shown to be the target of Pdr3p to elevate the level of PDR5 transcription. Finally, we provide evidence in the absence of PDR1 for a PDR3-controlled transcriptional induction of the drug pump by cycloheximide and propose a model for the mechanism governing the transcriptional autoregulation of Pdr3p.
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PMID:Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance. 762

AbrB is a transcriptional regulator of many Bacillus subtilis genes. A number of AbrB-binding sites have previously been delimited by DNase I footprinting studies, but the heterogeneity of the protected sequences and sizes has not led to a determination of a possible consensus motif for recognition. We have examined the affinity of AbrB for binding to six known target regions when the regions were placed in DNA fragments of various sizes. The sites are shown to vary dramatically in AbrB-binding affinity when they are present in smaller fragments, but the differences are smaller when the affinities of larger fragments are compared. Additional observations that indicate that AbrB binding may be a multistep cooperative process are reported.
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PMID:In vitro binding affinity of the Bacillus subtilis AbrB protein to six different DNA target regions. 763 37

OxyR is a redox-sensitive transcriptional regulator of the LysR family which activates the expression of genes important for the defense against hydrogen peroxide in Escherichia coli and Samonella typhimurium. OxyR is sensitive to oxidation and reduction, and only oxidized OxyR is able to activate transcription of its target genes. Using site-directed mutagenesis, we found that one cysteine residue (C-199) is critical for the redox sensitivity of OxyR, and a C-199-->S mutation appears to lock the OxyR protein in the reduced form. We also used a random mutagenesis approach to isolate eight constitutively active mutants. All of the mutations are located in the C-terminal half of the protein, and four of the mutations map near the critical C-199 residue. In vivo as well as in vitro transcription experiments showed that the constitutive mutant proteins were able to activate transcription under both oxidizing and reducing conditions, and DNase I footprints showed that this activation is due to the ability of the mutant proteins to induce cooperative binding of RNA polymerase. Unexpectedly, RNA polymerase was also found to reciprocally affect OxyR binding.
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PMID:Mutational analysis of the redox-sensitive transcriptional regulator OxyR: regions important for oxidation and transcriptional activation. 786 2

Transcription of virulence genes of Bordetella pertussis is co-ordinately regulated by the BvgA and BvgS proteins, which are members of the two-component family of bacterial signal-transduction proteins. BvgS is the transmembrane sensor and BvgA the transcriptional regulator. By gel mobility shift assays we demonstrate that phosphorylated BvgA (BvgA approximately P) forms distinct complexes with the filamentous haemagglutinin (PFHA) promoter DNA at different BvgA approximately P: DNA ratios. DNase I protection analyses show that phosphorylation of BvgA not only enhances affinity of the protein for the binding sites of the PFHA and bvgP1 promoters, but it extends significantly the bound region towards position -35 of these promoters. Conversely, a 10-fold higher amount of BvgA approximately P is required for binding to a large DNA region, from -168 to -60, of the pertussis toxin (Ptox) promoter sequence. These findings suggest that the molecular interaction of BvgA approximately P with the Ptox promoter is different from its interaction with the PFHA and bvgP1 promoters. The sigma 70 Escherichia coli RNA polymerase (RNP) does not bind to the bvg-regulated promoters. However, following the formation of a BvgA approximately P-promoter complex, the E. coli RNP specifically recognizes and binds to the bvg-regulated promoters. Thus, BvgA approximately P exerts its action at the level of promoter recognition by directing promoter selectivity by RNP.
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PMID:Differential binding of BvgA to two classes of virulence genes of Bordetella pertussis directs promoter selectivity by RNA polymerase. 886 79


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