Alexander Kel

SITEVIDEO: a computer system for functional site analysis and recognition. Investigation of the human splice sites

We developed the computer system SITEVIDEO for analysis and recognition of the functional sites in DNA and RNA molecules. It reveals contextual features essential for site function and thus enable the user to design efficient methods for recognition of the functional sites. We mainly considered only quantitative characteristics reflecting the uneven distribution of oligonucleotides in the sequences of functional sites of interest. The approach suggested makes use of available information about the hierarchical organization of the functional sites, and ensures highly precise prediction of the sites. The present analysis is concerned with the human donor and acceptor splice sites. A method for recognizing these sites in the sequences with an accuracy of approximately 90% was developed.

Molecular genetic characterization of the regulatory region of the Xist gene in the common vole Microtus rossiaemeridionalis

Two conserved regions were identified as a result of interspecific comparison of the 5′-region of the Xist gene, which is the key player in the process of X-chromosome inactivation in mammalian females. The first region corresponds to the minimal promoter, and the second spans between −480 bp and −400 bp from the start of Xist transcription. Footprinting experiments revealed protected regions corresponding to the potential binding sites for TBP, SP1, AP1, SRY, ER, and some other transcription factors. They also demonstrated the interaction with the minimal promoter of the human recombinant transcription factor SP1 in vitro and of the transcription factor CTCF in vivo. Experiments with reporter constructs showed that repressors of Xist transcription were located between −100 bp and −200 bp and between −300 bp and −400 bp and activators of Xist transcription were located between −200 bp and −300 bp and between −400 bp and −500 bp.

Comparative analysis of the DXPas34 regulatory region in rodents

Mouse X chromosome inactivation center contains the DXPas34 minisatellite locus which plays an important role in expression regulation of the Tsix and Xist genes, involved into female dosage compensation. Comparative analysis of the DXPas34 locus from mouse, rat, and four common vole species revealed similar organization of this region in the form of tandem repeat blocks. A search for functionally important elements in this locus showed that all the species examined carried the conservative motif monomers, which could be involved in regulation of X inactivation.

Simulation of the Dynamics of Gene Networks Regulating the Cell Cycle in Mammalian Cells

The study of the molecular mechanisms determining cellular programs of proliferation, differentiation, and apoptosis is currently attracting much attention. Recent studies have demonstrated that the system of cell-cycle control based on the transcriptional regulation of the expression of specific genes is responsible for the transition between programs. These groups of functionally connected genes form so-called gene networks characterized by numerous feedbacks and a complex behavioral dynamics. Computer simulation methods have been applied to studying the dynamics of gene networks regulating the cell cycle of vertebrates. The data on the regulation of the key genes obtained from the CYCLE-TRRD database have been used as a basis to construct gene networks of different degrees of complexity controlling the G1/S transition, one of the most important stages of the cell cycle. The behavior dynamics of the model constructed has been analyzed. Two qualitatively different functional modes of the system has been obtained. It has been shown that the transition between these modes depends on the duration of the proliferation signal. It has also been demonstrated that the additional feedback from factor E2F to genes c-fos and c-jun, which was predicted earlier based on the computer analysis of promoters, plays an important role in the transition of the cell to theS phase.

Transcription Factor Databases

Abstract Information about transcription factors and their genomic sites of action are stored in dedicated databases, TFDBs (transcription factor databases). They maybe accompanied by models about the DNA-binding domains of the transcription factors and models describing their DNA-binding specificity. These models may be provided for descriptive as well as for predictive purposes. In this article, we describe these features of TFDBs in more details, exemplify them with some of the most popular databases in use, and give an overview of those resources that are actively maintained at present.