T V Busygina

Institute of Cytology and Genetics, Novo-Nikolaevsk, Novosibirsk, Russia

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Publications (13)23.02 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The transcription factor SF-1 (steroidogenic factor 1) regulates the expression of the steroidogenesis genes, coordinates the development and function of the hypothalamic-pituitary-gonadal and adrenal systems, and plays an important role in the development and function of the reproductive system. SF-1 belongs to the superfamily of nuclear receptors and activates gene expression via binding as a monomer to DNA. The SiteGA method was developed for recognizing the binding sites for SF-1. The method utilizes a genetic algorithm and discriminant analysis to identify the context features of extended (93-bp) regions harboring the SF-1 sites in a training sample. Recognition of the SF-1 sites showed that the SiteGA method allows more reliable predictions as compared to the common weight matrix method. Experimental verification of 18 putative SF-1 sites predicted for the regulatory regions of the steroidogenesis genes showed that 15 (83%) of them did indeed interact with SF-1. The density of putative SF-1 sites was analyzed in the regulatory regions of genes from various functional groups, and new target genes of SF-1 were sought in the human genome. The potential targets of SF-1 include the genes coding for cytokine receptors, growth factor receptors, and proteins involved in the corresponding signal transduction pathways, as well as genes expressed in the epididymis. Expression of SF-1 in the epididymis was predicted and verified experimentally.
    Molecular Biology 01/2006; 40(3):454-464. · 0.64 Impact Factor
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    ABSTRACT: Development of computational methods to search for transcription factor binding sites (TFBSs) is important in investigation of regulatory regions of eukaryotic genes and in genome annotation. We propose a SiteGA method for recognition of TFBSs, providing the search of SF-1 binding sites as an example. The SiteGA method was implemented using a genetic algorithm (GA) involving an iterative discriminant analysis of local dinucleotide context characteristics. These characteristics were compiled not only over the core binding site (BS) region, but over its flanks as well. The major advancement of this approach is an improvement in accuracy by a large window capturing the meaningful context features besides the canonical consensus. The experimental verification confirmed the majority of predicted sites. The program SiteGA is available at http://wwwmgs2.bionet.nsc.ru/mgs/programs/sitega/.
    12/2005: pages 31-41;
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    ABSTRACT: Using gel retardation of DNA samples and specific antibodies, binding sites for the transcription factor SF-1 were found in positions -53/-44 and -285/-270 in the promoter region of the mouse Cyp17 gene and in position -117/-108 of the promoter region of the mouse 3betaHSDI gene.
    Biochemistry (Moscow) 11/2005; 70(10):1152-6. · 1.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Using gel retardation of DNA samples and specific antibodies, binding sites for the transcription factor SF-1 were found in positions −53/−44-and −285/−270 in the promoter region of the mouse Cyp17 gene and in position −117/−108 of the promoter region of the mouse 3βHSDI gene.
    Biochemistry (Moscow) 01/2005; 70(10):1152-1156. · 1.15 Impact Factor
  • T V Busygina, E V Ignatieva, A V Osadchuk
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    ABSTRACT: Using 42 nucleotide sequences extracted from the Transcription Regulatory Regions Database (TRRD) containing SF-1 transcription factor binding site, we have determined the decanucleotide (GTCAAGGTCA) consensus sequence for SF-1 binding. In the frequency matrix of this sequence nucleotides between the 3rd and the 7th position had the highest frequency and guanine nucleotides at the 6th and the 7th positions were recognized in all nucleotide sequences. The latter suggests a crucial role of these guanines for the interaction of DNA with SF-1 protein. The determined consensus and frequency matrix were used for search of putative SF-1 binding sites in regulatory regions of two genes, encoding mouse Cyp17 (17alpha-hydroxylase/17-20-lyase) and 3betaHSDI (3beta-hydroxysteroid dehydrogenase/4delta-5delta-isomerase I), the microsomal enzymes involved in steroidogenesis. 5;-Flanking regions of genes encoding Cyp17 and 3betaHSDI were shown to contain six and five such binding sites, respectively. The presence of the putative SF-1 binding sites in the regulatory regions of mouse Cyp17 and 3betaHSDI suggests that gene SF-1 could represent one of the putative genes which (as we predicted earlier) determine coordinated inheritable variability of hormonal activity in mouse Leydig cells.
    Biochemistry (Moscow) 05/2003; 68(4):377-84. · 1.15 Impact Factor
  • T.V. Busygina, E.V. Ignatieva, A.V. Osadchuk
    [Show abstract] [Hide abstract]
    ABSTRACT: Using 42 nucleotide sequences extracted from the Transcription Regulatory Regions Database (TRRD) containing SF-1 transcription factor binding site, we have determined the decanucleotide (GTCAAGGTCA) consensus sequence for SF-1 binding. In the frequency matrix of this sequence nucleotides between the 3rd and the 7th position had the highest frequency and guanine nucleotides at the 6th and the 7th positions were recognized in all nucleotide sequences. The latter suggests a crucial role of these guanines for the interaction of DNA with SF-1 protein. The determined consensus and frequency matrix were used for search of putative SF-1 binding sites in regulatory regions of two genes, encoding mouse Cyp17 (17α-hydroxylase/17-20-lyase) and 3HSDI (3-hydroxysteroid dehydrogenase/4Δ-5Δ-isomerase I), the microsomal enzymes involved in steroidogenesis. 5'-Flanking regions of genes encoding Cyp17 and 3HSDI were shown to contain six and five such binding sites, respectively. The presence of the putative SF-1 binding sites in the regulatory regions of mouse Cyp17 and 3HSDI suggests that gene SF-1 could represent one of the putative genes which (as we predicted earlier) determine coordinated inheritable variability of hormonal activity in mouse Leydig cells.
    Biochemistry (Moscow) 01/2003; 68(4). · 1.15 Impact Factor
  • T. V. Busygina, A. V. Osadchuk
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    ABSTRACT: Several steps of cAMP- and substrate-dependent testosterone production in the testes were studied with laboratory mouse micropopulations of six inbred strains (A/He, CBA/Lac, C57Bl/6J, DD, YT, PP). The strains differed in basal testosterone production in the gonads and in its response to activation of the adenylate cyclase signal transduction pathway at various steps by human chorionic gonadotropin (hCG), the cholera toxin, forskolin, and dibutyryl-cAMP and in the presence of pregnenolone, an early precursor of testosterone. Establishment of dominant–subordinate relationships in mouse populations substantially affected testosterone production in response to all activators of testicular steroidogenesis. The secretory activity of the testes decreased at the early establishment of social hierarchy in experimental micropopulations, then returned to the initial level, and again decreased in the case of activation with hCG, dibutyryl-cAMP, and pregnenolone. With all activators of steroidogenesis, basal and activated testosterone production changed in the same direction during the establishment and maintenance of social hierarchy, suggesting coordinated changes in all examined steps of testosterone biosynthesis in the testes. The among-strain differences in response to all activators of steroidogenesis remained much the same at various stages of the establishment of social hierarchy. The parameters of cAMP- and substrate-dependent testosterone production averaged over individual stages of the establishment of social hierarchy proved associated. Their genotypic correlations were positive and, in many cases, significant. Subsequent component analysis showed that one principal component accounted for more than 80% of the total among-strain variation, suggesting a coordinated genetic control of the endocrine function of the testes.
    Russian Journal of Genetics 04/2001; 37(5):528-534. · 0.43 Impact Factor
  • T V Busygina, A V Osadchuk
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    ABSTRACT: Micropopulations consisting of six male mice of different genotypes were studied (each of lines A/He, CBA/Lac, C57BL/6J, DD, YT, and PT was represented by one male). Interlinear differences in the level of social dominance and the effects of genotype, social hierarchy, and season on in vitro testosterone production by testes were examined under different incubation conditions. The testosterone production was estimated under control conditions and under stimulation with human chorionic gonadotropin (CG). Significant genetic differences in the initial and CG-stimulated testosterone production by testes incubated in vitro were found. By the control production, the genotypes fell into two groups: lines C57BL/6J, A/He, and CBA/Lac had low production of the hormone; lines YT, PT, and DD, high production. By responsiveness of gonads to CG, the genotypes fell into three groups: line CBA/Lac had low testosterone production by testes; lines C57BL/6J, A/He, YT, and DD, line PT, intermediate production; and line PT, high production. The obtained data indicate stability of genetic polymorphism for the responsiveness of testes to gonadotropins, because neither season nor the formation of social hierarchy could significantly change the interlinear differences. In line PT characterized by high hormonal activity of gonads in the control and under stimulation with gonadotropins, males became dominant in a significantly greater number of cases studied during the formation of hierarchy in micropopulations. The dynamics of both control production of a male sex hormone and responsiveness of testes to CG was established in vitro during the formation of social hierarchy; the effects of season on this dynamics were revealed. Specific characteristics of secretory activity of testes were detected in the control and under stimulation with gonadotropins, depending on incubation conditions. Seasonal and genotypic characteristics of the responsiveness of testes to CG were revealed under different incubation conditions. Genotypic characteristics indicate interlinear differences in the degree of inertia of testosterone biosynthesis on exposure to gonadotropins.
    Genetika 02/2001; 37(1):97-106. · 0.37 Impact Factor
  • T. V. Busygina, A. V. Osadchuk
    [Show abstract] [Hide abstract]
    ABSTRACT: Micropopulations consisting of six male mice of different genotypes were studied (each of lines A/He, CBA/Lac, C57BL/6J, DD, YT, and PT was represented by one male). Interlinear differences in the level of social dominance and the effects of genotype, social hierarchy, and season on in vitro testosterone production by testes were examined under different incubation conditions. The testosterone production was estimated under control conditions and under stimulation with human chorionic gonadotropin (CG). Significant genetic differences in the initial and CG-stimulated testosterone production by testes incubated in vitro were found. By the control production, the genotypes fell into two groups: lines C57BL/6J, A/He, and CBA/Lac had low production of the hormone; lines YT, PT, and DD, high production. By responsiveness of gonads to CG, the genotypes fell into three groups: line CBA/Lac had low testosterone production by testes; lines C57BL/6J, A/He, YT, and DD, line PT, intermediate production; and line PT, high production. The obtained data indicate stability of genetic polymorphism for the responsiveness of testes to gonadotropins, because neither season nor the formation of social hierarchy could significantly change the interlinear differences. In line PT characterized by high hormonal activity of gonads in the control and under stimulation with gonadotropins, males became dominant in a significantly greater number of cases studied during the formation of hierarchy in micropopulations. The dynamics of both control production of a male sex hormone and responsiveness of testes to CG was established in vitro during the formation of social hierarchy; the effects of season on this dynamics were revealed. Specific characteristics of secretory activity of testes were detected in the control and under stimulation with gonadotropins, depending on incubation conditions. Seasonal and genotypic characteristics of the responsiveness of testes to CG were revealed under different incubation conditions. Genotypic characteristics indicate interlinear differences in the degree of inertia of testosterone biosynthesis on exposure to gonadotropins.
    Russian Journal of Genetics 12/2000; 37(1):85-93. · 0.43 Impact Factor
  • Source
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    ABSTRACT: 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/
    Nucleic Acids Research 02/2000; 28(1):298-301. · 8.28 Impact Factor
  • Source
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    ABSTRACT: 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/
    Nucleic Acids Research 02/1999; 27(1):303-6. · 8.28 Impact Factor
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    ABSTRACT: The SF-1 (Steroidogenic Factor-1) is a transcription factor known as a key regulator of the steroidogenic gene expression. SF-1 is required for the development and functioning at all levels of the hypothalamic-pituitary-gonadal and adrenal axis. Also it plays an essential role in sex determination. SF-1 is a member of the nuclear receptor superfamily and it activates gene expression by binding to DNA in a monomeric form. Here, we report the results of potential SF-1 binding sites identification by using the SiteGA recognition method. The SiteGA method was implemented using a genetic algorithm (GA) involving a iterative discriminant analyses of local dinucleotide context characteristics. These characteristics were compiled not only over the core binding sites region but over its flanks as well. Developed SiteGA method is characterized by considerably better recognition accuracy when compared to that for the weight matrix method. The experimental tests demonstrated that 83% of the sites recognized by the SiteGA method in the regulatory regions of steroidogenic genes, indeed, interact with the SF-1 factor. We also estimated the density of predicted sites in regulatory region of genes, the members of different functional groups and developed the criterion to search for new SF-1 target genes in genome sequences.
    Molekuliarnaia biologiia 40(3):512-23.
  • K V Svechnikov, T V Busygina, A V Osadchuk
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    ABSTRACT: A very effective procedure was developed for separation of sex hormones of the delta 4 pathway using the microcolumn technique of high performance liquid chromatography (HPLC). A five-step gradient containing methanol, acetonitrile and water was used as a mobile phase, while Lychrosorb RP-18 with particles of 5 microns was used as a sorbent. Metabolism of steroid hormones and activity of 3 beta-steroid dehydrogenase, 17 alpha-hydroxylase, C17-20-lyase and 17-ketosteroid reductase were studied in Leydig cells of two mouse strains PT and A/He. The higher rate of steroid metabolism and of the enzymatic activity was detected in the mouse cells of PT strain as compared with those of A/He strain.
    Voprosy medit͡sinskoĭ khimii 40(4):14-7.

Publication Stats

63 Citations
23.02 Total Impact Points

Institutions

  • 2003–2006
    • Institute of Cytology and Genetics
      Novo-Nikolaevsk, Novosibirsk, Russia
  • 2001–2005
    • Russian Academy of Sciences
      • Institute of Cytology and Genetics, Siberian Branch
      Moskva, Moscow, Russia