["Co-phased blocks"--conservative regions of double-stranded DNA of transcriptional regulatory modules--are close in space due to phasing at nucleosome DNA super helix].

Conservative regions varying in length from 30 to 70 nucleotides (nt) are revealed as a result of interspecies comparison of homologous nucleotide sequences of the loci, genes controlling early development in Drosophila species. These regions are observed at the intermediate level between transcription factor binding sites (usually about 7-10 nt) and the nucleosome repeat unit (165-210 nt). Segments found are located mainly in the area of known functional elements of the locus (cis-regulatory modules: enhancers, a proximal promoter, a coding segment). Conservative domains occupy less than a half of the full enhancer length and contain practically all annotated transcription factor binding sites. A quasi periodical pattern of conservative region disposition is in accord with the experimental nucleosome localization pattern. The distance between neighboring domains is about 84 nt, i.e. a pitch of nucleosome DNA super helix. A repeatable accuracy of the distance permits of treating the delineated conservative regions as co-phased blocks and stating that these domains are close in the space being located at neighboring coils of the nucleosome DNA super helix.

[Mutual disposition of nucleosomes and exons differs from common genome pattern at DNA segments containing periodic nucleotide sequences].

The correlation was observed between DNA segments characterized by periodic patterns of nucleotides and nucleosome DNA binding sites predicted by the profiles of local DNA flexibility. Exons of human type I and VII collagen genes loci have been chosen as a sample set of periodic DNA segments. It was pointed that short periodic exons coding fibrillar part of these proteins are localized near borders of the DNA sequence that binds the histone core. One of the borders of exon and of this sequence coincide as a rule. In non-fibrillar parts of collagen genes exons (longer on average) dispose, in contrast, in any place of the DNA sequence bound to the nucleosome core.

[Correlations between clusters of protein-DNA binding sites and the binding experimental data allow to predict a structure of regulatory modules].

Here we analyzed an option to predict the structure of cis-regulatory modules that consist of binding sites of different proteins (heterogeneous cis-regulatory modules) using mutual positional correlations between protein-DNA binding experimental data and computationally identified clusters of binding sites for each of the proteins.

[Preferred distances between DNA binding sites for factors regulating transcription initiation].

Transcriptional regulation of gene expression in higher eukaryotes is driven by sophisticated protein complexes of transcription factors. On the DNA level, there are composite elements containing sites of different DNA-binding proteins. We use the hypoxia-response system to identify preferred localization distances for the 'hypoxia-induced factor-1 binding site-co-factor binding site" pairs in promoter DNA regions of the human genome. Such characteristic colocalization distances agree with the supposed scale of regulatory regions, while being significantly longer than the typical binding site length. We speculate that this phenomenon can provide a key to decipher the structure of DNA regulatory regions of higher eukaryotes.

[Using the operonic gene pairs for establishing the treshold for correlation coefficient of differently expressed genes].

We developed an approach for effective estimating the correlations in the noise component of gene expression data. An efficent noise reduction technique has been suggested. The resulting technique has been applied to E. coli microarray data and tested on SOS response modulated genes.

[Asymmetry of the GC content in vicinity of transcription starts (with participation of polymerase PoII) and its correlation with location of adsorption sites of protein SP1 on DNA].

Nucleotide DNA sequences within the clusters of transcription starts, determined by the method of cap analysis of gene expression, have some distinguishing features. The sequences of these clusters are rich in nucleotides C and G, and there is an asymmetry of the nucleotide content, which correlates with the choice of chain from which the transcription in the cluster occurs. On the coding chain, the concentration of guanine exceeds the concentration of cytosine. In the nucleotide sequence of the cluster on the coding chain, the frequency of the polynucleotide tracts of the avoided nucleotide (cytosine), normalized to the frequency expected based on the content of this nucleotide in the cluster, is significantly higher compared with the normalized frequency of the polynucleotide tracts of the other nucleotide (guanine). Similarly, the statistical significance of the C-rich variant of the site of specific binding of the transcription initiation factor Sp1 in the coding chain is higher than that of the G-rich variant. However, the assumption can hardly be confirmed that the choice of the variant of the binding region of protein Sp1 correlates with the choice of the transcription chain. It is more likely that both variants are more or less equally probable, and the binding region of protein Sp1 acts in this case as a factor of selection, which counteracts the mutations inducing the shift of the nucleotide content.

[Left helix of polyproline II type and genesis of beta-structures in spidroins 1 and 2 and their recombinant analogs].

The distribution of secondary structures along the polypeptide chains of spider proteins spidroins 1 and 2 and their recombinant analogs has been studied by statistical methods. It was found that these proteins in the monomolecular form contain only trace amounts of beta-structures. At the same time, the regions of the sequence including Ala and Gly are predicted as helical-containing (with alpha-helices and left-helices of polyproline II type). An analysis of literature data and our data obtained in this study shows that the main conformation of the polypeptide chain solutions of spidroins 1 and 2 and their recombinant analogs in water solutions is the left-helix of polyproline II type with some contaminations of alpha-helices and a very small share of beta-structures. The transition to the state with extended conformations, which are peculiar to mature filaments of spider webs, requires the dehydration of the polypeptide chain backbone. Thus, the genesis of beta-structure in spider web proteins is determined by the conditions of conformation transitions between the main regular conformations of the polypeptide chain backbone.

[Integration of data obtained by different experimental methods to determine the motifs in DNA sequences recognized by transcription-regulating factors].

For 39 proteins regulating the transcription of Drosophila melanogaster, refined motifs typical for nucleotide sequences specifically interacting with these proteins have been constructed using the new logarithm ChiPMunk. The entire spectrum of available experimental data, including the data of DNAse footprinting, SELEX, ChIP-chip, and B1H-system, has been used. Motifs constructed by integrating the data obtained by independent experimental methods show the highest sensitivity. The collection of motifs can be used to refine the immediate binding sites of transcription factors in DNA nucleotide sequences. The collection of motifs and the results of the estimation of motif quality are available at: http://line.imb.ac.ru/iDMMPMM. The realization of the algorithm ChIPmunk is accessible at http://line.imb.ac.ru/Chipmunk.

[Application of noninteracting probes in the protein structure space for the construction of statistical potentials for atom-atom interactions].

Some effects hindering the construction of knowledge-based potentials of atom-atom interactions in problems of biopolymer modeling have been considered. It was shown that some limitations are overcome by considering the distribution of distances between noninteracting probes in the protein structure space. It was shown that knowledge-based potentials thus constructed can be effectively used to analyze the hydration of protein atoms. Using this approach, it is possible to predict the structure water location in a protein globule and recognize the correctly folded protein structure among decoys.

[Nucleosomal repeat and the location of exons and introns in genes of collagens types I and VII].

Regions with a quasiperiodical location of exon--intron sites have been found in the loci of genes of I and VII type collagens (with a total length of exons more than 15% of the entire size of the locus). The periods observed are similar to periods typical for the nucleosomal level of the organization of chromatin. It was shown that the sites consisting of successively arranged exons and introns form groups involving two to five such regions of the same length. The groups encoding the fibrillar regions of the gene product contain more than 50% of exons. The regions are on the average 165 nt long, which is close to the minimal nucleosomal repeat length observed in some regions of the eukaryotic genome. In the nonfibrillar region of the gene of VII type collagen, groups of several exon-intron pairs with an average length of 227 nt were identified. The change in the length of exon-introns sites on going from the nonfibrillar to the fibrillar moiety occurs in a jump, which is clearly seen on a periodogram of the locus.

[Relationship between micro- and minisatellites in the human genome].

Micro- and minisatellites constitute an essential part of DNA with a low sequence complexity and carry several important functions. A search for tandem repeats in the human genome with a length of a repeat unit of up to 70 bp, including repeats with a great number of nucleotide substitutions, has been performed using the TaadeaSWAN program. It was shown that, for a considerable number of minisatellites with the length of the repeating unit of less than 25 nt, a shorter repeating motif can be distinguished in the sequence of this repeat, which often is similar to the sequence of minisatellites widely occurring in the human genome. A model of hierarchic origination of minisatellites in the human genome is suggested.

[ClusterTree-RS: the binary tree algorithm for identification of co-regulated genes by clustering regulatory signals].

Identification of groups of co-regulated genes (regulons) is an important part of studying transcriptional regulation. One possible approach is to cluster regulatory sites that were found using experimental or computational techniques, such as phylogenetic footprinting. This strategy doesn't require a priori knowledge about co-regulation and allows finding putative new members of known groups of co-regulated genes (i.e. a new regulon). Also, it allows finding new putative regulons, which is especially important for poorly annotated genomes. We have developed ClusterTree-RS, an algorithm for clustering regulatory signals using binary trees; it is presented in this paper along with some testing results on simulated and real data. The algorithm is implemented in Java and took about 2 hours 40 minutes to cluster 1500 input signals on a computer with AMD Athlon 1.91 GHz CPU.

[A study of periodicity in the primary structure of spidroin 1 and spidroin 2 from spiders belonging to various species]. / Issledovanie periodichnostei v posledovatel'nostiakh aminokislot spidroinov pervogo i vtorogo tipov iz paukov razlichnykh vidov.

Sequences of spidroin 1 and 2 from spiders belonging to various species were analyzed by Fourier analysis. Specific periodical patterns were found in various segments of the sequences. These characteristic periodicities vary within the same proteins as well as between spidroin 1 and spidroin 2 sequences. It is possible that alterations in periodicity help to recognize contact sites between the molecules. Spidroins of 2 type have similar sequence structure consisting of four parts with a particular periodical pattern. These parts are a constant C-terminal part, a long-periodical part, a short-periodical part, and a constant N-terminal part.

[An analysis of the secondary structure of spider spidroins I and II belonging to different species]. / Analiz vtorichnykh struktur spidroinov pervogo i vtorogo tipov iz paukov, prinadlezhashchikh razlichnym vidam.

We have analyzed the secondary structure of spidroin proteins of I and II types, related to spiders of different species. We used standard methods of secondary structure prediction NNPREDICT and JPRED and also analyzed the occurrences of oligopeptides with a preferred secondary structure with the help of the OLIGON program. We have demonstrated that local segments of the polypeptide chain can adopt alpha- and beta-conformations as well as the left-handed helix of polyproline II type. Periodical patterns found in the amino acid distribution indicate that there is a possibility of development of a macroscopic order accompanied by local conformational transitions.

[Similarities in periodical structures in the position of nucleotides in regions of initiation of replication of bacterial genomes]. / Skhodstvo periodicheskikh struktur v raspolozhenii nukleotidov na uchastkakh nachala replikatsii bakterial'nykh genomov.

The regions of initiation of replication of some bacterial genomes were studied by the method of Fourier matrix analysis. A generalized spectral portrait of the primary structures of E. coli-like regions of initiation of replication in bacteria was obtained, which reflects the features of their structural and functional organization. It contains well-pronounced peaks that correspond to the periods T = 2, 11, 17, 27, 86-105 of nucleotides. The peaks corresponding to T = 9, 13, 14, 18, 19, 33-35, 45-47, 74-85, 106-110 are less pronounced. The uniqueness of the Fourier spectrum corresponding to the region of initiation of replication of E. coli oriC was considered by the example of the complete genome of E. coli. Some regions of the E. coli genome were identified that differ from oriC in the primary structure but have Fourier spectra resembling the spectrum of oriC. A number of these regions are alternative points of initiation of replication in sdrA(rnh) mutants of E. coli, the others are localized in yet unidentified regions of the E. coli genome but are capable, in our opinion, to participate in the initiation of replication. Thus, from the similarity of spectral portraits of different regions of the genome, it was possible to reveal several regions that have similar functions, i.e., are involved in initiation of replication.

[Analysis of peculiarities in nucleotides disposition in the origin of chromosome replication-oriC from Escherichia coli]. / Analiz osobennostei raspredeleniia nukleotidov na uchastke nachala replikatsii khromosomy-oriC iz Escherichia coli.

Along with symmetrical features (palindromes, direct and inverted repeats), periodicities in the disposition of nucleotides in the origin of chromosome replication oriC from E. coli were studied by means of Fourier analysis. Peaks corresponding to the periods T = 2, 17, 95-100 nucleotides are the highest in the Fourier spectrum of oriC. Peaks corresponding to the periods T = 3, 11, 19, 13, 24, 27, 28, 41, 79-81 nucleotides are also prominent, but not so high. Thus, the main periodicities of the oriC spectrum of are not multiple of the B-DNA sugar-phosphate backbone period, which destabilize DNA at oriC and contributes to the spontaneous unwinding of DNA. The differences between the Fourier spectrum of oriC and those of regions adjacent to oriC are demonstrated.

[Statistical analysis of the exon-intron structure of higher eukaryote genes]. / Statisticheskii analiz ékzon-intronnoi struktury genov vysshikh éukariot.

The exon-intron structure of human, insect (Drosophila sp.), and dicot plant (Arabidopsis thaliana) genes was considered. In each genome there exists a characteristic intron length. Anomalously long introns was usually the first introns in genes. In each sample there are correlations between the lengths of neighboring exons and between exon lengths and closeness to the consensus of the sites at exon boundaries. Exons and exon pairs containing an integer number of triplets are preferred. These results are relevant to the study of splicing mechanism and evolution of introns, as well as construction of gene recognition algorithms.

[Periodicity in contacts of RNA-polymerase with promotors]. / Periodichnosti v kontaktakh RNK-polimerazy s promotorami.

Periodicities in the position of E.coli RNA polymerase promoter contacts on several promoters (lacUV5, T7 A3, tetR, lambda cin, lambda c17, RNA1, and trp S.t.) were found by means of Fourier analysis. The comparison of the Fourier spectrum of core RNA polymerase contacts on the lacUV5 promoter and that of holoenzyme revealed a more prominent 7-periodicity in the Fourier spectrum of holoenzyme contacts. 6-, 7-, and 8-periodicities were found in the primary structure of the majority of E.coli promoters. It is shown that RNA polymerase recognizes specific periodic patterns in the promoter structure.

[Fourier analysis of nucleotide sequences. Periodicity in E. coli promoter sequences]. / Fur'e-analiz nukleotidnykh posledovatel'nostei. Periodichnosti v promoternykh posledovatel'nostiakh E. coli.

Fourier spectra of E. coli promoter DNA sequences have been obtained. The periodical structure of individual promoter sequences is characterized. E. coli promoter sequences are classified according to their Fourier spectra using three feature sets: 1--the number of peaks in Fourier spectra; 2--values of power spectra for promoter primary structures and their similarity with physical periodicities in the backbone of polynucleotide; 3--the presence of blocks made of equal nucleotides. The comparison of Fourier spectra of promoter sequences and corresponding genes is provided. The conclusion that different ways of stabilization of promoter secondary structure in the case of different primary structure periodicities is drawn. The intermittence of AT- and GC-blocks, and variety of Fourier spectra mean DNA hydrate shell in DNA promoters is non-contiguous and non-stable at junction points. Characteristic features of prokaryotic promoters Fourier spectra differ from human promoters.

[Statistics of periodic regularities in sequences of human introns]. / Statistika periodicheskikh zakonomernostei v posledovatel'nostiakh intronov cheloveka.

A formula for the calculation of average power of a Fourier harmonic of a nucleotide sequence with given composition by means of the matrix Fourier analysis method is suggested. A search for the periodic regularities with the periods from two to ten nucleotides was carried out on a sample set of human exons and introns. It is shown that all the periodicities researched, including the three nucleotides period, are random in introns, whereas in exons the 3 periodic regularity is much stronger. The periods that are not multiples of 3, however, are also random in exons. The two nucleotides periodicity, which is, according to the literature, over-represented in introns, appears to be also random in the case under study. The results are important for the development of the algorithms for the coding regions search in DNA, and for the understanding of the global statistic regularities in human genome.