A relational database of transcription factors

Ghosh, Debjani

doi:10.1093/nar/18.7.1749

Cited by 194 publications

(70 citation statements)

References 67 publications

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“…The 85-bp sequence in pGC7-8.0 that confers iron-repressible transcription on downstream elements of a CYCI-lacZ fusion contains a 12-bp direct repeat, TlTIT'GCTCAYC, located 3' to the RAPI binding site. A search of sequence motifs for the recognition sites of DNA-binding proteins failed to reveal any match with this repeated sequence (32). Inserting sequences to positions -208 or -176 resulted in an increased range of regulation by iron similar to that seen for the larger promoter fragments in pGC6-9 and pJ105, and thus a second iron-control element may be present 3' of -255.…”

Section: Resultsmentioning

confidence: 87%

Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron.

Dancis¹,

Roman²,

Anderson³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

311

222

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The principal iron uptake system of Saccharomyces cerevisiae utilizes a reductase activity that acts on ferric iron chelates external to the cell. The FREI gene product is required for this activity. Iron is an essential nutrient that is required by many enzymes for cellular functions such as DNA synthesis and respiration. Ferric iron forms insoluble ferric hydroxide complexes in the presence of oxygen and water, making iron availability a biological problem under these conditions. Ferrous iron is much more soluble but is rapidly converted to ferric iron in the presence of oxygen (1). Cells have developed two major solutions to the problem of assimilation offerric iron from the environment. In Escherichia coli, specific ferric binding compounds termed siderophores are secreted that bind and solubilize environmental iron and deliver it to specific receptors for transport across the outer and inner membranes (2). In the yeast Saccharomyces cerevisiae, the major iron uptake system under aerobic conditions depends on a transplasma membrane electron transport system (3, 4) that reduces ferric iron external to the cell. Multicellular eukaryotes may also use an externally directed ferric reductase prior to transmembrane movement of ferrous iron (5-8). Our previous results indicated that the FREI gene product in S. cerevisiae is required for external ferric reduction and for ferric iron utilization, thus linking these two processes (9). However, a mutation in FREI did not affect the uptake offerrous iron (9), suggesting that the ferrous transport system is an independent component of the iron utilization apparatus in yeast. Many organisms control their rate of iron assimilation by ascertaining their requirement for iron and expressing a limiting component of the uptake system accordingly (10). Our previous results suggest that during aerobic growth of S. cerevisiae, changes in iron availability are reflected in alterations in the levels of FREI mRNA and of ferric iron uptake (9). In this paper we present the structure of the FREI gene and identify DNA sequences that mediate its regulation by ironA MATERIALS AND METHODSYeast Strains. The following yeast strains were derived from the wild-type strain F113 (MATa, can), inol-13, ura3-52): W103 (MATa, can], inol-13, ura3-52,frel-1) was derived by chemical mutagenesis of F113 and selection for a reductase-negative phenotype (9); W126 was derived by transformation of F113 with the plasmid pWDC20, which carries the FREI gene on the high-copy-number vector YEp24 (11). We used one-step gene disruption (12) to create strain N1 (MATa, can), inol-13, Afrel:: URA3), in which an 800-base-pair (bp) Xho I fragment internal to the FREI coding region was replaced with a URA3 marker gene, and strain N2 (MATa, can, inol-13, Afrel:: URA3), in which a 2.7-kilobase (kb) Cla I fragment containing the entire FREI coding region was similarly replaced. Disruption/deletion strains of the FREI locus were also constructed in the wild-type strain H1085, yielding strain W218 (MATa, leu2-3,112, ...

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Section: Resultsmentioning

confidence: 87%

Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron.

Dancis¹,

Roman²,

Anderson³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

311

222

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“…Therefore, it is critical to substantially reduce the search space for functional cis-element clusters prior to wholegenome examination. We have therefore sought to do this in the context phylogeny and compositional similarity within a sequence window of 200 bp that is appropriate for local ciselement interactions.Attempts to find putative TF-binding sites in regulatory DNA sequences began with a database of TF-binding-site sequences (Ghosh 1990) and a program developed to scan a DNA sequence against that database (Prestridge 1991). Since then, several programs have been developed to analyze DNA sequences against TF-binding-site sequence databases.…”

mentioning

confidence: 99%

“…Attempts to find putative TF-binding sites in regulatory DNA sequences began with a database of TF-binding-site sequences (Ghosh 1990) and a program developed to scan a DNA sequence against that database (Prestridge 1991). Since then, several programs have been developed to analyze DNA sequences against TF-binding-site sequence databases.…”

mentioning

confidence: 99%

Detection and Visualization of Compositionally Similar cis-Regulatory Element Clusters in Orthologous and Coordinately Controlled Genes

Jegga

Sherwood²,

Carman³

et al. 2002

Genome Res.

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Evolutionarily conserved noncoding genomic sequences represent a potentially rich source for the discovery of gene regulatory regions. However, detecting and visualizing compositionally similar cis-element clusters in the context of conserved sequences is challenging. We have explored potential solutions and developed an algorithm and visualization method that combines the results of conserved sequence analyses (BLASTZ) with those of transcription factor binding site analyses (MatInspector) (http://trafac.chmcc.org). We define hits as the density of co-occurring cis-element transcription factor (TF)-binding sites measured within a 200-bp moving average window through phylogenetically conserved regions. The results are depicted as a Regulogram, in which the hit count is plotted as a function of position within each of the two genomic regions of the aligned orthologs. Within a high-scoring region, the relative arrangement of shared cis-elements within compositionally similar TF-binding site clusters is depicted in a Trafacgram. On the basis of analyses of several training data sets, the approach also allows for the detection of similarities in composition and relative arrangement of cis-element clusters within nonorthologous genes, promoters, and enhancers that exhibit coordinate regulatory properties. Known functional regulatory regions of nonorthologous and less-conserved orthologous genes frequently showed cis-element shuffling, demonstrating that compositional similarity can be more sensitive than sequence similarity. These results show that combining sequence similarity with cis-element compositional similarity provides a powerful aid for the identification of potential control regions.In higher multicellular organisms, cell-type-specific nuclear machinery has an uncanny ability to direct precise patterns of gene expression through the recognition of arrays of ciselements specified by primary DNA sequence lying in the context of higher-order chromatin structure. Computationally, however, we have little ability to identify cis-regulatory regions from primary sequence and even less ability to predict cellular compartments into which expression is specified. Improved ability to do so will advance our understanding of eukaryotic gene regulatory mechanisms, facilitate improved annotation of the genome, and provide insight into the potential effects of sequence polymorphisms on gene expression patterns. Moreover, improved understanding of cis-element clusters present in coordinately regulated gene groups may allow for the prediction of gene regulatory network behaviors during development, homeostasis, and disease. To exploit the potential power of conserved cis-element clusters to contribute to our understanding of eukaryotic gene regulation, it is critical to create database resources from multiple sequence analysis methods on the basis of both phylogenetic conservation and known binding-site matches that can be mined for patterns that correlate with experimentally gathered expression profile data. As shown by man...

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“…CRV105 is unique in two respects: it has duplicated S-block sequences and a 1 bp deletion in the O-block. The integrated BKT-1B NCCR is heavily rearranged and only distantly related to any previously * Sequence analysis was performed using the GCG Sequence Analysis Software Package 7.3 (Ghosh, 1990). Analysis allowing no mismatches was used to identify the transcription factor binding sites created at junctions between the sequence blocks.…”

Section: The B K V Stock Preparation Is Heterogeneous and Contains Atmentioning

confidence: 99%

“…The model assumes that an archetypal, BKV (WW)-like, strain has been present in the viral stock at some earlier stage of the passage history (see Discussion). For the sake of completeness, the variant PQ has been (Ghosh, 1990) included in the model. However, a recombinant BKV with this NCCR does not grow in Vero cells.…”

Section: The Evolution and Sequence Characteristics Of The New Bkv Ncmentioning

confidence: 99%

Subpopulations of non-coding control region variants within a cell culture-passaged stock of BK virus: sequence comparisons and biological characteristics

Johnsen¹,

Seternes²,

Johansen

et al. 1995

Journal of General Virology

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In the circular DNA genome of the human polyomavirus BK an approximately 400 bp non-coding control region (NCCR) separates the early and late genes. The NCCR contains the origin of replication as well as the promoter/enhancer with a mosaic of cis-acting elements involved in the regulation of both early and late transcription. The NCCR has been shown to be very heterogeneous between different BK virus (BKV) strains. This may affect the host cell permissivity and oncogenic potential of a given BKV strain. Our previous studies with BKT-1B, a continuous cell line established from a BKV (Gardner) -induced hamster fibrosarcoma, revealed that the BKV DNA is integrated in the host genome in multiple copies. The sequence of the integrated BKV NCCR was substantially different from (and even contained sequences not found in) that of the BKV (Gardner) strain supposedly used to establish the BKT-1B cell line. PCR amplification, cloning and subsequent sequencing revealed that the original BKV (Gardner) stock contained at least seven different subpopulations of viral genomes. None of them had a control region 'anatomy' which was identical to either the BKV (Gardner) strain, the variant found integrated in BKT-1B cells or any previously published NCCR. In order to study the biological significance of these new BKV NCCR variants we developed a simple cassette model allowing the NCCRs of the new variants to be cloned in an identical genomic background of BKV protein-coding sequences and performed transfection studies with the recombinant genomes in non-permissive rodent cells and in semi-permissive monkey cells. The results demonstrated that the NCCR variants conferred striking differences, in both transforming capacity and host cell permissivity, to the recombinant BKV genomes. Sequence comparisons suggested genetic explanations for these differences, as well as evolutionary relationships between BKV NCCRs.

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A relational database of transcription factors

Cited by 194 publications

References 67 publications

Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron.

Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron.

Detection and Visualization of Compositionally Similar cis-Regulatory Element Clusters in Orthologous and Coordinately Controlled Genes

Subpopulations of non-coding control region variants within a cell culture-passaged stock of BK virus: sequence comparisons and biological characteristics

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