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T I Merkulova

Publications and source records attributed to T I Merkulova.

At least 19 recordsLinked to original sources
PubMed2002

Transcription Regulatory Regions Database (TRRD): its status in 2002.

Transcription Regulatory Regions Database (TRRD) is an informational resource containing an integrated description of the gene transcription regulation. An entry of the database corresponds to a gene and contains the data on localization and functions of the transcription regulatory regions as well as gene expression patterns. TRRD contains only experimental data that are inputted into the database through annotating scientific publication. TRRD release 6.0 comprises the information on 1167 genes, 5537 transcription factor binding sites, 1714 regulatory regions, 14 locus control regions and 5335 expression patterns obtained through annotating 3898 scientific papers. This information is arranged in seven databases: TRRDGENES (general gene description), TRRDLCR (locus control regions); TRRDUNITS (regulatory regions: promoters, enhancers, silencers, etc.), TRRDSITES (transcription factor binding sites), TRRDFACTORS (transcription factors), TRRDEXP (expression patterns) and TRRDBIB (experimental publications). Sequence Retrieval System (SRS) is used as a basic tool for navigating and searching TRRD and integrating it with external informational and software resources. The visualization tool, TRRD Viewer, provides the information representation in a form of maps of gene regulatory regions. The option allowing nucleotide sequences to be searched for according to their homology using BLAST is also included. TRRD is available at http://www.bionet.nsc.ru/trrd/.

Animals↗
PubMed2001

rSNP_Guide, a database system for analysis of transcription factor binding to target sequences: application to SNPs and site-directed mutations.

rSNP_Guide is a novel curated database system for analysis of transcription factor (TF) binding to target sequences in regulatory gene regions altered by mutations. It accumulates experimental data on naturally occurring site variants in regulatory gene regions and site-directed mutations. This database system also contains the web tools for SNP analysis, i.e., active applet applying weight matrices to predict the regulatory site candidates altered by a mutation. The current version of the rSNP_Guide is supplemented by six sub-databases: (i) rSNP_DB, on DNA-protein interaction caused by mutation; (ii) SYSTEM, on experimental systems; (iii) rSNP_BIB, on citations to original publications; (iv) SAMPLES, on experimentally identified sequences of known regulatory sites; (v) MATRIX, on weight matrices of known TF sites; (vi) rSNP_Report, on characteristic examples of successful rSNP_Tools implementation. These databases are useful for the analysis of natural SNPs and site-directed mutations. The databases are available through the Web, http://wwwmgs.bionet.nsc.ru/mgs/systems/rsnp/.

Binding Sites↗
PubMed2001

Involvement of transcription factor HNF3gamma in the effect of o-aminoazotoluene on glucocorticoid induction of tyrosine aminotransferase in mice sensitive to its hepatocarcinogenic action.

In the rodent liver, hepatocarcinogens inhibit the glucocorticoid induction of several liver-specific genes, including tyrosine aminotransferase (TAT). A distinct positive correlation exists in mice between the extent of inhibition of TAT induction after acute administration of o-aminoazotoluene (OAT) and the frequency of liver tumors after chronic exposure to the carcinogen. To elucidate the mechanism of the carcinogenic action, the effects of OAT on the DNA-binding activity of several transcription factors participating in the glucocorticoid regulation of TAT gene expression were studied. The experimental inbred male mice were sensitive (A/He and SWR/J, tumor induction frequency of 75-100%, TAT induction inhibition of 35-50%) and resistant (CC57BR/Mv and AKR/J, 0-6% and 10-15%, respectively) to OAT. Gel retardation experiments showed that hepatocyte nuclear factor 3 (HNF3)gamma DNA-binding activity was strongly reduced in nuclear extracts from the livers of OAT-treated A/He and SWR/J mice but only slightly reduced in CC57Br/Mv and AKR/J mice. The DNA-binding activities of Ets, AP1 family members, and GME binding proteins were unaffected. HNF3gamma DNA-binding activity was reduced by 1 h after OAT administration and remained low for 1 mo, as did inhibition of TAT induction in the liver. These results suggested that the inhibitory effect of OAT on the glucocorticoid induction of TAT is mediated by reduced HNF3gamma DNA-binding activity.

Animals↗
PubMed2001

[Formation of transcription factors AP-1 during learning in Helix].

An increase in the DNA-binding activity for the AP-1-family factors was shown to occur after food aversion conditioning. Learning experiments in vitro enhanced the DNA-binding activity. Effects of simultaneous action of serotonine and calcium on activation of transcriptional AP-1 factors was suppressed by inhibitor of calcium/calmodulin-dependent protein-kinases KN62 as well as by inhibitor of MAP-kinases PD98059. The co-operative induction of transcriptional AP-1 family factors activation by serotonine-induced and calcium-dependent regulatory systems may be one of the mechanisms of aversive conditioning in the CNS of the land snail.

Animals↗
PubMed2000

Transcription regulatory regions database (TRRD): its status in 2000.

Transcription Regulatory Regions Database (TRRD) has been developed for accumulation of experimental information on the structure-function features of regulatory regions of eukaryotic genes. Each entry in TRRD corresponds to a particular gene and contains a description of structure-function features of its regulatory regions (transcription factor binding sites, promoters, enhancers, silencers, etc.) and gene expression regulation patterns. The current release, TRRD 4.2.5, comprises the description of 760 genes, 3403 expression patterns, and >4600 regulatory elements including 3604 transcription factor binding sites, 600 promoters and 152 enhancers. This information was obtained through annotation of 2537 scientific publications. TRRD 4.2.5 is available through the WWW at http://wwwmgs.bionet.nsc.ru/mgs/dbases/trrd4/

Databases, Factual↗
PubMed2000

Translation termination in eukaryotes: polypeptide release factor eRF1 is composed of functionally and structurally distinct domains.

Class-1 polypeptide chain release factors (RFs) trigger hydrolysis of peptidyl-tRNA at the ribosomal peptidyl transferase center mediated by one of the three termination codons. In eukaryotes, apart from catalyzing the translation termination reaction, eRF1 binds to and activates another factor, eRF3, which is a ribosome-dependent and eRF1-dependent GTPase. Because peptidyl-tRNA hydrolysis and GTP hydrolysis could be uncoupled in vitro, we suggest that the two main functions of eRF1 are associated with different domains of the eRF1 protein. We show here by deletion analysis that human eRF1 is composed of two physically separated and functionally distinct domains. The "core" domain is fully competent in ribosome binding and termination-codon-dependent peptidyl-tRNA hydrolysis, and encompasses the N-terminal and middle parts of the polypeptide chain. The C-terminal one-third of eRF1 binds to eRF3 in vivo in the absence of the core domain, but both domains are required to activate eRF3 GTPase in the ribosome. The calculated isoelectric points of the core and C domains are 9.74 and 4.23, respectively. This highly uneven charge distribution between the two domains implies that electrostatic interdomain interaction may affect the eRF1 binding to the ribosome and eRF3, its activity in the termination reaction and activation of eRF3 GTPase. The positively charged core of eRF1 may interact with negatively charged rRNA and peptidyl-tRNA phosphate backbones at the ribosomal eRF1 binding site and exhibit RNA-binding ability. The structural and functional dissimilarity of the core and eRF3-binding domains implies that evolutionarily eRF1 originated as a product of gene fusion.

Amino Acid Sequence↗
PubMed1999

Point mutations within 663-666 bp of intron 6 of the human TDO2 gene, associated with a number of psychiatric disorders, damage the YY-1 transcription factor binding site.

Single base mutations G-->A at position 663 and G-->T at position 666 of intron 6 of the human tryptophan oxygenase gene (TDO2) are associated with a variety of psychiatric disorders [Comings, D.E. et al. (1996) Pharmacogenetics 6, 307-318]. Binding of rat liver nuclear extract proteins to synthetic double-strand oligonucleotides corresponding to three allelic states of the region between 651 bp and 680 bp of human TDO2 intron 6 has been studied by gel shift assay. It has been demonstrated that to each allelic state of the region there corresponds a specific set of proteins that interacts with it. With the aid of computer analysis and using specific anti-YY-1 antibodies it has been shown that both mutations damage the YY-1 transcription factor binding site.

Animals↗
PubMed1999

C-terminal domains of human translation termination factors eRF1 and eRF3 mediate their in vivo interaction.

At the termination step of protein synthesis, hydrolysis of the peptidyl-tRNA is jointly catalysed at the ribosome by the termination codon and the polypeptide release factor (eRF1 in eukaryotes). eRF1 forms in vivo and in vitro a stable complex with release factor eRF3, an eRF1-dependent and ribosome-dependent GTPase. The role of the eRF1-eRF3 complex in translation remains unclear. We have undertaken a systematic analysis of the interactions between the human eRF1 and eRF3 employing a yeast two-hybrid assay. We show that the N-terminal parts of eRF1 (positions 1-280) and of eRF3 (positions 1477) are either not involved or non-essential for binding. Two regions in each factor are critical for mutual binding: positions 478-530 and 628-637 of eRF3 and positions 281-305 and 411-415 of eRF1. The GTP binding domain of eRF3 is not involved in complex formation with eRF1. The GILRY pentamer (positions 411-415) conserved in eukaryotes and archaebacteria is critical for eRF1's ability to stimulate eRF3 GTPase. The human eRF1 lacking 22 C-terminal amino acids remains active as a release factor and promotes an eRF3 GTPase activity whereas C-terminally truncated eRF3 is inactive as a GTPase.

Amino Acid Sequence↗
PubMed1999

Transcription Regulatory Regions Database (TRRD):its status in 1999.

The Transcription Regulatory Regions Database (TRRD) is a curated database designed for accumulation of experimental data on extended regulatory regions of eukaryotic genes, the regulatory elements they contain, i.e., transcription factor binding sites, promoters, enhancers, silencers, etc., and expression patterns of the genes. Release 4.1 of TRRD offers a number of significant improvements, in particular, a more detailed description of transcription factor binding sites, transcription factors per se, and gene expression patterns in a computer-readable format. In addition, the new TRRD release provides considerably more references to other molecular biological databases. TRRD 4.1 is installed under SRS and is available through the WWW at http://www.bionet.nsc.ru/trrd/

Animals↗
PubMed1998

Functional expression of eukaryotic polypeptide chain release factors 1 and 3 by means of baculovirus/insect cells and complex formation between the factors.

Translation termination in eukaryotes is governed by termination codons in mRNA and two release factors, eRF1 and eRF3. In this work, human eRF1 and eRF3 have been produced in insect cells using a recombinant baculovirus expression system for the corresponding human cDNAs. Purification of eRF1 has led to a homogeneous 50-kDa protein active in promoting ribosome-dependent and termination-codon-dependent hydrolysis of formylmethionyl-tRNAf(Met). Purification of eRF3 yielded a full-length protein and shorter polypeptides. Microsequencing of the N-terminus of the shortest form detected a site of proteolytic cleavage between Arg91 and Gly92, probably due to exposed region(s) hypersensitive to proteolysis. The mixture of full-length and truncated forms of eRF3 as well as bacterially expressed eRF3 lacking 138 N-terminal amino acids (eRF3Cp) are active as an eRF1-dependent and ribosome-dependent GTPase and in stimulating the GTP-dependent release activity of eRF1. Complex formation between eRF1 and eRF3Cp was demonstrated by affinity and gel-filtration chromatographies and by native-gel electrophoresis. An abnormal electrophoretic mobility observed for eRF1 as compared with the complex points to a significant conformational change of either eRF1 or both factors in the complex. Co-expression of both factors in baculovirus-infected insect cells and a yeast two-hybrid assay were applied to monitor complex formation in vivo. In yeast cells, both eRF1 and eRF3 are either in a monomeric or in a heterodimeric but not in a homodimeric state.

Amino Acid Sequence↗
PubMed1998

GeneExpress: a computer system for description, analysis, and recognition of regulatory sequences in eukaryotic genome.

GeneExpress system has been designed to integrate description, analysis, and recognition of eukaryotic regulatory sequences. The system includes 5 basic units: (1) GeneNet contains an object-oriented database for accumulation of data on gene networks and signal transduction pathways and a Java-based viewer that allows an exploration and visualization of the GeneNet information; (2) Transcription Regulation combines the database on transcription regulatory regions of eukaryotic genes (TRRD) and TRRD Viewer; (3) Transcription Factor Binding Site Recognition contains a compilation of transcription factor binding sites (TFBSC) and programs for their analysis and recognition; (4) mRNA Translation is designed for analysis of structural and contextual features of mRNA 5'UTRs and prediction of their translation efficiency; and (5) ACTIVITY is the module for analysis and site activity prediction of a given nucleotide sequence. Integration of the databases in the GeneExpress is based on the Sequence Retrieval System (SRS) created in the European Bioinformatics Institute.

Artificial Intelligence↗
PubMed1995

Monoclonal antibodies directed against unique and common determinants on the lipopolysaccharide molecule of Salmonella serogroups A, B, and D.

A panel of monoclonal antibodies (MAbs) directed against lipopolysaccharide (LPS) of Salmonella serogroups A, B, and D was generated. Nine most productive hybrid clones were selected from several fusions of mouse myeloma cells with splenocytes from BALB/c mice, immunized with the corresponding heat-killed bacteria. The MAbs were characterized by enzyme immunoassay, Western blot analysis, and dot-immunoblotting with LPS and whole bacteria of Salmonella serogroups A-E and some other representatives of the Enterobacteriaceae family. Seven MAbs were reactive with the sole Salmonella strain used as an immunogen; one MAb, SD:10D9H, reacted with the five major serogroups of Salmonella species (A, B, D, E1, and E2); and one MAb, SA:5D12A, reacted with Salmonella serogroups A-E and a rough strain of S. cholerae-suis. None of the MAbs reacted with LPS of E. coli 055:B5 or whole bacteria of E. coli K12, Klebsiella pneumoniae, or Proteus vulgaris. The typical ladder-like patterns of bands were observed after immunoblotting of MAbs against electrophoretically resolved LPS from Salmonella serogroups A-E, which thus confirmed their LPS-directed specificity. MAbs affinity constants were determined by noncompetitive enzyme immunoassay using serial dilutions of both LPS as antigen (coating the plate) and antibodies. On the base of the results obtained, the presumed epitopes for each of the MAbs were discussed. The usefulness of MAbs generated for diagnostic and protective purposes was declared.

Animals↗
PubMed1994

The immediate vicinity of mouse metallothionein-I gene contains two sites conferring glucocorticoid inducibility to the heterologous promoter.

Glucocorticoid responsive elements (GREs) located -252 to -209 by upstream and +1011 to +1054 bp downstream of the transcription initiation site of the mouse metallothionein-I (mMT-I) gene were identified in transient experiments. However, the promoter region of the mMT-I gene (-330 to +70 bp) was found to provide low, if any, glucocorticoid induction of the linked CAT gene, while showing strong cadmium regulation, comparable with the in vivo level.

Animals↗
PubMed1991

Glucocorticoid-receptor binding sites at the 5' flanking region of a rat cytochrome CYP2B2 gene predicted with a novel computer method.

Using an original computer method to search for potential DNA binding sites for glucocorticoid-receptor complexes (GRC) (Seledtsov, I.A., Solovjev, V.V. and Merkulova, T.I. (1991) Biochim. Biophys. Acta 1089, 367-376), the presence of two such sites in the 5' flanking region of a rat cytochrome CYP2B2 gene has been predicted. This prediction has been confirmed by gel retardation experiments.

Animals↗